Cancer Res Treat [JOURNAL]
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200 papers
A Phase II Study of Bendamustine Plus Rituximab in Patients with Relapsed or Progressive Marginal Zone Lymphoma: KCSG LY14-09.
Lee JO, Park J, Kang HJ … +7 more , Hyun SY, Lee GW, Yhim HY, Kim HJ, Lee JS, Heo DS, Kim TM
Cancer Res Treat · 2025 Dec · PMID 41381062 · Publisher ↗
PURPOSE: This multicenter, phase II study examined the efficacy and safety of bendamustine plus rituximab in patients with relapsed or progressive marginal zone lymphoma (MZL). MATERIALS AND METHODS: Patients received si...
PURPOSE: This multicenter, phase II study examined the efficacy and safety of bendamustine plus rituximab in patients with relapsed or progressive marginal zone lymphoma (MZL). MATERIALS AND METHODS: Patients received six cycles of bendamustine 90 mg/m2 intravenously on days 2 and 3, rituximab 375 mg/m2 intravenously in cycle 1, and 1,400 mg subcutaneously in cycles 2-8 on day 1 every 4 weeks. Bendamustine dose reduction to 60 mg/m2 (level -1) and 40 mg/m2 (level -2) was allowed based on prespecified toxicity criteria. The primary endpoint was overall response rate (ORR) and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Among the 26 evaluable patients, 81.8% achieved an ORR, while 40.7% had a complete response. The median PFS was 46.06 months, and the estimated 3-year OS rate was 92.3%. Hematological toxicities, primarily neutropenia (grade 3/4, 48.1%), were the most common adverse events, resulting in both reduction and interruption of bendamustine doses, accounting for 18 (75%) of 24 dose-reduced cycles and 7 (41%) of 17 missed cycles, respectively. Nonhematologic toxicities were generally mild, with nausea and fatigue identified as the most frequently reported toxicities. The mean relative dose intensities were 76.9% (range, 31.5-100) for bendamustine and 91.3% (range, 72.7-100) for rituximab. CONCLUSION: Bendamustine plus rituximab is a highly effective and tolerable treatment for patients with relapsed or progressive MZL, providing durable disease control.
ITGB2 Gene Gain as a Prognostic Marker for Early Recurrence in Luminal HER2-Negative High Proliferative Breast Cancer.
Liu CY, Chen JL, Tsai YF … +8 more , Chao TC, Wang WL, Lien PJ, Hsu CY, Lai JI, Huang CC, Chiu JH, Tseng LM
Cancer Res Treat · 2025 Dec · PMID 41381061 · Publisher ↗
PURPOSE: Early recurrence reflects aggressive disease and poor prognosis, with patterns varying across breast cancer subtypes. Early recurrence is a major challenge in luminal HER2-negative high proliferative breast canc...
PURPOSE: Early recurrence reflects aggressive disease and poor prognosis, with patterns varying across breast cancer subtypes. Early recurrence is a major challenge in luminal HER2-negative high proliferative breast cancer, yet reliable biomarkers remain limited. Identifying biomarkers associated with early recurrence is therefore of significant interest. MATERIALS AND METHODS: Forty-two patients with stage I-III luminal HER2-negative, high-proliferative breast cancer were enrolled in the VGHTPE cohort and underwent targeted next-generation sequencing using the ACTOnco Comprehensive Cancer Panel. Findings were validated in The Cancer Genome Atlas (TCGA) and METABRIC datasets, and in vitro experiments were conducted to assess cell aggressiveness. RESULTS: We examined 42 patients, including 15 who experienced recurrence within five years and 27 who did not. Next-generation sequencing revealed that the most prevalent alterations in this luminal HER2-negative, high-proliferative breast cancer cohort were mutations in PIK3CA and TP53, and amplifications/gains in MCL1, MYC, and KLF6. Patients with recurrence within five years exhibited a higher frequency of ITGB2 gain compared with non-recurrent patients. Validation in the TCGA and METABRIC cohorts confirmed the prognostic significance of ITGB2 gain in ER+/HER2- breast cancers. Gene Set Enrichment Analysis indicated that high ITGB2 expression was enriched in KRAS and EMT pathways. In vitro experiments further demonstrated that ITGB2 knockdown led to inactivation of Akt and ERK signaling and suppression of cell aggressiveness in ER+/HER2- breast cancer cells. CONCLUSION: ITGB2 gain represents an unfavorable prognostic marker for early recurrence in luminal HER2-negative high proliferative breast cancer, with potential therapeutic implications.
Zolbetuximab Plus Chemotherapy as First-Line Treatment in Patients with Claudin 18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma: Korean Population Subgroup-Combined Efficacy and Safety Analysis from SPOTLIGHT and GLOW.
Lee KW, Oh SC, Kim JG … +16 more , Sym SJ, Shim BY, Kang SY, Kim IH, Kim JH, Chon HJ, Cho SH, Song EK, Oh DY, Kim JS, Park YI, Kang WK, Kim HD, Lee J, Yi M, Ryu MH
Cancer Res Treat · 2025 Dec · PMID 41381060 · Publisher ↗
PURPOSE: The phase 3 SPOTLIGHT and GLOW trials, in patients with claudin 18 isoform 2-positive, human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal j...
PURPOSE: The phase 3 SPOTLIGHT and GLOW trials, in patients with claudin 18 isoform 2-positive, human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) and overall survival (OS) with first-line zolbetuximab plus chemotherapy versus placebo plus chemotherapy. This analysis evaluated efficacy and safety in the Korean subgroup from SPOTLIGHT and GLOW. MATERIALS AND METHODS: Patients were randomized 1:1 to receive zolbetuximab plus chemotherapy or placebo plus chemotherapy (mFOLFOX6 [modified folinic acid, 5-fluorouracil, and oxaliplatin] or CAPOX [capecitabine and oxaliplatin]). Primary endpoint was PFS, assessed per RECIST v1.1 by independent review committee. Other efficacy and safety parameters were assessed. RESULTS: The Korean subgroup consisted of 49 patients in the zolbetuximab group and 47 in the placebo group. Median PFS (95% confidence interval [CI]) was 12.3 months (7.3-15.3), and median OS was 30.5 months (16.1-45.5) with zolbetuximab versus 8.1 months (4.2-10.4) and 15.8 months (11.8-19.7) with placebo, respectively. Most common TEAEs in patients who received zolbetuximab versus placebo were nausea (79.6% vs. 53.2%), vomiting (55.1% vs. 21.3%), and decreased appetite (53.1% vs. 23.4%). Treatment-related TEAEs led to discontinuation of zolbetuximab and placebo in 4.1% and 2.1% of patients, respectively. CONCLUSION: Zolbetuximab plus chemotherapy demonstrated favorable PFS and OS versus placebo plus chemotherapy in the Korean subgroup, with numerically greater efficacy compared with the overall pooled population. This may be potentially attributable to low rates of zolbetuximab discontinuation and toxicity management.
Silence of Transmembrane Channel-Like 5 Inhibits Cell Proliferation, Migration, and Invasion While Promoting Apoptosis Via Deactivating the AKT Pathway in Breast Cancer.
Wan J, Li Y, Liu Z
Cancer Res Treat · 2025 Dec · PMID 41381059 · Publisher ↗
PURPOSE: Transmembrane channel-like 5 (TMC5) plays a tumor-promoting role in the progression of various tumors. However, its effect on regulating breast cancer cell function remains scarce. The current study aimed to eva...
PURPOSE: Transmembrane channel-like 5 (TMC5) plays a tumor-promoting role in the progression of various tumors. However, its effect on regulating breast cancer cell function remains scarce. The current study aimed to evaluate the effect of TMC5 silence on the proliferation, apoptosis, migration, and invasion of breast cancer cell lines. MATERIALS AND METHODS: TMC5-specific small interfering RNA (siTMC5) and siNC were transfected into MDA-MB-231 and MCF-7 cell lines; subsequently, the 740Y-P was co-cultured. Then, the proliferation, apoptosis, migration, invasion, and p-AKT expression were determined. RESULTS: In MDA-MB-231 and MCF-7 cell lines, silence of TMC5 could reduce the proliferation rate at 48 hours (h) and 72 h, migration rate, and invasion rate, while elevate the apoptosis rate. Besides, silence of TMC5 could decrease the p-AKT/AKT expression. The combination of 740Y-P with the silence of TMC5 could reversely increase the proliferation rate at 48h and 72h, migration rate, and invasion rate compared with the silence of TMC5 only. The apoptosis rate showed the opposite trend. CONCLUSION: The silence of TMC5 could inhibit the proliferation, migration, and invasion while promoting the apoptosis of breast cancer, while more in vivo validation is needed to explore its potential to be a treatment target for patients with breast cancer.
Kidney Failure-Related Mortality in Patients with Cancer: Insights from the Cancer Public Library Database in South Korea.
Kim CS, Suh SH, Choi HS … +6 more , Bae EH, Ma SK, Jung JH, Kim B, Han KD, Kim SW
Cancer Res Treat · 2025 Nov · PMID 41289714 · Publisher ↗
PURPOSE: Kidney failure is associated with an increased risk of death. However, since the impact of kidney failure on overall and cancer-related mortality among individuals with cancer remains unclear, we investigated ki...
PURPOSE: Kidney failure is associated with an increased risk of death. However, since the impact of kidney failure on overall and cancer-related mortality among individuals with cancer remains unclear, we investigated kidney failure-related mortality in patients with cancer, stratified by various cancer types. MATERIALS AND METHODS: A total of 1,307,680 participants newly diagnosed with cancer were identified from the Cancer Public Library Database. We analyzed data from patients with preexisting kidney failure before cancer diagnosis and compared their mortality risk with patients without kidney failure using multivariable Cox proportional hazard models. RESULTS: All-cause and cancer-related mortality was significantly higher in the kidney failure group. Preexisting kidney failure was associated with an increased risk of mortality in all cancer types after adjusting for comorbidities and treatment modalities (adjusted hazard ratio [aHR] of all-cause death 1.75, 95% CI 1.70-1.81; aHR of cancer-related death 1.27, 95% CI 1.22-1.32). Among specific cancer types, thyroid and breast cancers showed the highest mortality risks of kidney failure, with thyroid cancer presenting the greatest risk. However, the risk of death was attenuated in liver, gallbladder, and lung cancers. Furthermore, aHRs were lower for mortality in metastatic cancer compared to localized and regional stages. CONCLUSION: Preexisting kidney failure significantly increases the risk of all-cause and cancer-related death among cancer patients, particularly in localized cancer and specific cancer types.
Association between FGFR2b Positivity and Survival Outcomes of Patients with Gastric Cancer Treated with First-Line Nivolumab Plus Chemotherapy.
Kim HD, Lee H, Lee H … +5 more , Moon M, Hyung J, Ma J, Park YS, Ryu MH
Cancer Res Treat · 2025 Nov · PMID 41289713 · Publisher ↗
PURPOSE: Fibroblast growth factor receptor 2b (FGFR2b) is a promising therapeutic target in gastric cancer; however, its clinical relevance in immune checkpoint inhibitor (ICI)-based chemotherapy remains unclear. Therefo...
PURPOSE: Fibroblast growth factor receptor 2b (FGFR2b) is a promising therapeutic target in gastric cancer; however, its clinical relevance in immune checkpoint inhibitor (ICI)-based chemotherapy remains unclear. Therefore, this study aims to evaluate the expression pattern and predictive value of FGFR2b in patients undergoing first-line nivolumab plus chemotherapy. MATERIALS AND METHODS: This single-center study included 503 patients diagnosed with gastric cancer. Among them, 296 underwent nivolumab-chemotherapy, while 207 underwent chemotherapy alone. FGFR2b expression was assessed via immunohistochemistry using samples collected after mid-2022. FGFR2b positivity was defined as membranous staining intensity of 2+/3+ in ≥ 1% of tumor cells, with ≥ 10% as overexpression, and 1-9% as low expression. RESULTS: FGFR2b overexpression and positivity were identified in 9.3% and 18.7% of cases, respectively. Discordance between paired biopsy and surgical samples was observed (20.0% and 40.0% for overexpression and positivity, respectively), indicating marked intratumoral heterogeneity. Among patients who underwent nivolumab-chemotherapy, FGFR2b overexpression and low expression were associated with favorable survival trends compared to those of FGFR2b-negative cases. These associations were not observed in patients treated with chemotherapy alone. Compared to chemotherapy alone, nivolumab-chemotherapy was associated with a greater survival benefit in patients with FGFR2b positivity. Multivariate interaction analyses revealed a significant interaction between FGFR2b expression and nivolumab-based chemotherapy. CONCLUSION: FGFR2b expression exhibits substantial intratumoral heterogeneity in gastric cancer and may be linked to favorable outcomes in patients undergoing first-line ICI plus chemotherapy. Therefore, future studies should validate this finding, along with mechanistic investigations.
Skeletal Muscle Index to Red Cell Distribution Width Ratio: A Novel Prognostic Indicator for Patients with Stage I-III Colorectal Cancer.
Choi J, Kang J
Cancer Res Treat · 2025 Nov · PMID 41265475 · Publisher ↗
PURPOSE: Herein, a novel prognostic marker based on the skeletal muscle index (SMI) and red cell distribution width (RDW) for patients with colorectal cancer (CRC) was developed. MATERIALS AND METHODS: 585 Patients with...
PURPOSE: Herein, a novel prognostic marker based on the skeletal muscle index (SMI) and red cell distribution width (RDW) for patients with colorectal cancer (CRC) was developed. MATERIALS AND METHODS: 585 Patients with stage I-III CRC who underwent surgery between January 2004 and April 2011 were included. The ratio of SMI to RDW (SRR) was calculated, and patients were grouped into sex-specific quartiles (G1 to G4) based on SRR. The Kaplan-Meier method was employed to estimate survival differences, and the Cox proportional hazards model was applied to evaluate the association between SRR and overall survival (OS). The Concordance Index (C-index) was calculated to assess the individual and combined effects of SMI and RDW on survival. RESULTS: There was a significant difference in OS across SRR quartiles (G1: 65.0%, G2: 82.9%, G3: 84.1%, G4: 89.8%, p<0.001). G1 had worse OS compared to the other groups, and SRR was confirmed as an independent prognostic factor for OS (G1 vs. G2, HR=0.531, 95% CI=0.320-0.882, p=0.014; G1 vs. G3, HR=0.534, 95% CI=0.302-0.942, p=0.030; G1 vs. G4, HR=0.419, 95% CI=0.212-0.827, p=0.012). SRR demonstrated greater prognostic power for OS than SMI or RDW alone. CONCLUSION: SRR is a novel and significant predictor of overall survival in patients with stages I-III CRC demonstrating greater prognostic power than either SMI or RDW alone.
Dual-Functional PTX@Fe₃O₄ Nanobubbles: A Novel Theranostic Platform for Enhanced Ultrasound Imaging and Controlled Drug Delivery in Breast Cancer.
Lv W, Ning X, Huang C … +6 more , Li X, Bai L, Wang X, Wang Z, Song Y, Liu H
Cancer Res Treat · 2025 Nov · PMID 41265474 · Publisher ↗
PURPOSE: This study aimed to develop a novel theranostic nanoplatform that integrates ultrasound imaging and controlled drug delivery for the treatment of breast cancer. METHODS: PTX@Fe₃O₄ nanobubbles (NBs) were synthesi...
PURPOSE: This study aimed to develop a novel theranostic nanoplatform that integrates ultrasound imaging and controlled drug delivery for the treatment of breast cancer. METHODS: PTX@Fe₃O₄ nanobubbles (NBs) were synthesised via microfluidics. Characterisation included transmission electron microscopy, dynamic light scattering, drug release kinetics, phantom imaging and biocompatibility assays in vitro and in mice. RESULTS: The NBs exhibited uniform size (178 ± 12 nm), high drug loading (8.3%) and pH/ultrasound-responsive release (68.2% at pH 5.5+US). Ultrasound signal enhancement correlated linearly with concentration (R² = 0.988), with imaging duration three times longer than SonoVue. The system exhibited minimal haemolysis (<2%) and low cytotoxicity and induced S-phase arrest (68.2%) in MCF-7 cells. No significant toxicity was observed in mice at 10 mg Fe/kg. CONCLUSION: PTX@Fe₃O₄ NBs represent a promising, biocompatible theranostic platform for image-guided breast cancer therapy.
The Application of Contrast-Enhanced Ultrasound Combined with Indocyanine Green Lymphography in the Management of Secondary Upper Limb Lymphedema.
Gong X, Wang L, Liu F … +5 more , Zhang J, Xiao H, Hou Y, Guo X, Liu Z
Cancer Res Treat · 2025 Nov · PMID 41265473 · Publisher ↗
PURPOSE: To assess the clinical efficacy of contrast-enhanced ultrasound (CEUS) combined with indocyanine green (ICG) lymphography for the treatment of breast cancer-related lymphedema (BCRL). MATERIALS AND METHODS: Fift...
PURPOSE: To assess the clinical efficacy of contrast-enhanced ultrasound (CEUS) combined with indocyanine green (ICG) lymphography for the treatment of breast cancer-related lymphedema (BCRL). MATERIALS AND METHODS: Fifty-two patients with BCRL who underwent lymphaticovenous anastomosis between March 2022 and March 2024 were enrolled, of whom 22 underwent preoperative functional lymphatic vessel localization using ICG lymphography alone and 30 received CEUS combined with ICG lymphography. Treatment efficacy was evaluated using bioimpedance spectroscopy for segmental water content analysis, calculation of the upper extremity lymphedema (UEL) index, and administration of the Lymphedema Quality of Life Questionnaire (LYMQOL). Surgical parameters were also analyzed. RESULTS: Baseline characteristics were comparable between the groups. However, at both 6 and 12 months postoperatively, patients in the CEUS+ICG group demonstrated significantly improved outcomes compared to those in the ICG-only group, including: Reduced segmental water differences (6 months: 344.3 vs. 474.6 mL, p=0.0221; 12 months: 284.3 vs. 403.6 mL, p=0.0156); Lower UEL index (6 months: 124.2 vs. 134.1, p=0.0010; 12 months: 123.8 vs. 131.9, p=0.0105); Improved LYMQOL scores (6 months: 48.7 vs. 56.6, p=0.0029; 12 months: 47.6 vs. 54.2, p=0.0065). Additionally, the CEUS+ICG group achieved a significantly higher anastomosis success rate (83.2% vs. 63.3%, p<0.001) and reduced procedural time per anastomosis (48.9 vs. 61.6 minutes, p=0.0021). CONCLUSION: The combination of CEUS and ICG-L is associated with precise preoperative lymphatic mapping, a reduction in unnecessary incisions, as well as better anastomosis success rates and postoperative decongestion outcomes.
Prognostic Factors for Relapse and the Role of Maintenance Therapy in Acute Promyelocytic Leukemia: A Real-World Multicenter Study in Korea.
Kwak K, Kim M, Shin D … +16 more , Kim C, Choi YS, Kang KW, Kim BS, Jeon MJ, Yu ES, Kim DS, Choi CW, Lee BH, Lee SR, Sung HJ, Lee CH, Ahn SY, Yhim HY, Ahn JS, Park Y
Cancer Res Treat · 2025 Nov · PMID 41223497 · Publisher ↗
PURPOSE: Acute promyelocytic leukemia (APL) is curable, but relapse remains a concern, particularly in patients treated with all-trans retinoic acid (ATRA) and chemotherapy-based regimens. The identification of prognosti...
PURPOSE: Acute promyelocytic leukemia (APL) is curable, but relapse remains a concern, particularly in patients treated with all-trans retinoic acid (ATRA) and chemotherapy-based regimens. The identification of prognostic factors for relapse is important for enhanced survival outcomes. MATERIALS AND METHODS: This retrospective multicenter study analyzed the clinical outcomes and prognostic factors for relapse in 286 Korean patients treated with ATRA and idarubicin-based chemotherapy protocols between 2002 and 2024. RESULTS: Propensity score-matched analysis revealed key prognostic factors, such as post-consolidation measurable residual disease (MRD) (hazard ratio [HR]: 20.16, p<0.001) and male sex (HR: 5.96; p=0.016). No significant benefit of ATRA-based maintenance therapy was observed in relapse-free survival, compared with observation alone. We also found that FLT3-internal tandem duplication (ITD) mutations were associated with an increased risk of relapse. CONCLUSION: These findings highlight prognostic factors for relapse and the importance of individualized therapeutic strategies for high-risk patients. Moreover, our findings indicate that post-consolidation MRD is the most significant predictor of relapse, emphasizing the need for molecular profiling and longitudinal monitoring. Future prospective studies should validate these prognostic markers and refine personalized therapeutic approaches for APL.
Changes in Uptake, Participant Disparities, and Screening Outcomes of the Korean National Lung Cancer Screening Program: A Five-Year Experience.
Choi CK, Lee NY, Suh M … +2 more , Choi KS, Kim Y
Cancer Res Treat · 2025 Nov · PMID 41223496 · Publisher ↗
PURPOSE: Low-dose computed tomography (LDCT) is effective in reducing lung cancer mortality among high-risk smokers. The Korean National Lung Cancer Screening Program (KNLCS), the world's first nationwide lung cancer scr...
PURPOSE: Low-dose computed tomography (LDCT) is effective in reducing lung cancer mortality among high-risk smokers. The Korean National Lung Cancer Screening Program (KNLCS), the world's first nationwide lung cancer screening initiative using LDCT, was launched in 2019. This study aimed to evaluate the KNLCS uptake rates in relation to participants' economic status and changes in positive screening rates across screening rounds. MATERIALS AND METHODS: Data from the National Health Insurance Service (NHIS) and National Cancer Screening Information System for 2019-2023 were analyzed. Eligible participants in the KNLCS were current smokers aged 54-74 years with a smoking history of at least 30 pack-years. The KNLCS provides counseling by physicians on screening results and smoking cessation. Screening uptake rates, counseling rates, and Lung CT Screening Reporting and Data System (Lung-RADS) distributions were assessed. RESULTS: Screening uptake rates increased from 24.7% in 2019 to 51.2% in 2023 (p < 0.001). Economic disparities were observed, with higher-income groups showing consistently higher uptake rates than lower-income group. Screening positive rates has been decreased from 9.1% in 2019 to 7.0% in 2023 according to increasing the proportion of subsequent screening participants. The inter-institutional variance in Lung-RADS category 4 decreased significantly over the years (p < 0.001). CONCLUSION: The KNLCS rapidly increased screening uptake rates by systematically inviting eligible participants. Positive screening rates decreased primarily due to a reduction in Lung-RADS category 3 findings in subsequent rounds.
Chemotherapy-Free Salvage Therapy with Rituximab, Lenalidomide, and Poseltinib in Relapsed or Refractory Primary Central Nervous System Lymphoma: A Multi-Center, Phase II Study.
Kim DH, An S, Ahn H … +8 more , Song H, Kang KW, Yoon SE, Kim SJ, Kim HJ, Koh Y, Yang DH, Consortium for Improving Survival of Lymphoma (CISL)
Cancer Res Treat · 2025 Nov · PMID 41223495 · Publisher ↗
PURPOSE: Relapsed or refractory (R/R) primary central nervous system lymphoma (PCNSL) is an aggressive malignancy for which salvage chemotherapy has limited efficacy. We conducted an investigator-initiated, single-arm, m...
PURPOSE: Relapsed or refractory (R/R) primary central nervous system lymphoma (PCNSL) is an aggressive malignancy for which salvage chemotherapy has limited efficacy. We conducted an investigator-initiated, single-arm, multicenter phase II trial to evaluate the efficacy and safety of a chemotherapy-free salvage regimen comprising rituximab, lenalidomide, and poseltinib (R2P) in patients with R/R PCNSL. MATERIALS AND METHODS: The R2P regimen consisted of two phases: six cycles of induction with rituximab, lenalidomide, and poseltinib, followed by three cycles of consolidation with lenalidomide and poseltinib. The primary endpoints were complete response rate (CRR) and overall response rate (ORR). Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 10 patients were enrolled (one withdrew before cycle 1; nine were evaluable for efficacy). The median age was 70 years (range, 53-75), and all had received methotrexate-based first-line chemotherapy. The ORR was 55.6%, and the CRR was 33.3%. The median PFS was 5.6 months, and the median OS was not reached. Next-generation sequencing was performed in four patients (three responders and one non-responder). CD79B missense mutations were identified in all three responders. A total of 11 adverse events (AEs) were observed in six patients. The most common AE was neutropenia (30.0%). The only grade ≥3 AE was a single case of grade 3 neutropenia. No dose modifications were required due to toxicity. CONCLUSION: Poseltinib in combination with lenalidomide and rituximab showed activity in patients with R/R PCNSL, warranting further investigation in larger studies.
PHF10 is a Novel Substrate of Keap1 to Protect Non-Small-Cell Lung Cancer (NSCLC) Cells Against Oxidative Stress and Confer Ferroptosis Resistance.
Lu X, Kang N, Chen Y … +5 more , Zhao X, Zhu D, Yang J, Yang Y, Xie H
Cancer Res Treat · 2025 Nov · PMID 41197527 · Publisher ↗
PURPOSE: Keap1 mutations mainly caused NRF2-dependent anti-oxidative stress responses, yet whether there are other downstream substrates and pathways remains unknown. This study aimed to uncover the role of Keap1 mutatio...
PURPOSE: Keap1 mutations mainly caused NRF2-dependent anti-oxidative stress responses, yet whether there are other downstream substrates and pathways remains unknown. This study aimed to uncover the role of Keap1 mutations in regulating PHF10-NRF2 axis in NSCLC and ferroptosis evasion. MATERIALS AND METHODS: Tandem affinity purification with mass spectrometry was used to screen peptides. Co-IP and ubiquitination assays were used to confirm the Keap1-PHF10 axis. A series of analyses in cell lines, patient samples, and xenograft models were conducted to uncover the functional dependency between Keap1 and NRF2. Transmission electron microscope was used to detect mitochondrion swelling under ferroptosis. RESULTS: Here, we reported that Keap1 binds and promotes polyubiquitination and degradation of PHF10, a subunit of the PBAF complex. NSCLC-associated Keap1 mutations are incapable of degrading PHF10, and thus induces PHF10 proteins stability. PHF10 ablation shows synthetic lethality in Keap1-deficient NSCLC cells. Mechanistically, PHF10 interacts with NRF2 to activate its downstream targets and enhance the NRF2-dependent anti-oxidative stress capacity in NSCLC. PHF10 recruits SMARCA2, one core cBAF subunit, to increase chromatin accessibility in NRF2-binding transcriptional regions. Cancer-associated Keap1 mutants confer resistance to ROS-induced cell death via accumulating PHF10-SMARCA2 complex. Increased PHF10 further induced ferroptosis resistance in Keap1-deficient NSCLC. Lastly, we utilized one small molecule inhibitor, SMARCA2-IN-8, to inhibit progression of Keap1-deficient NSCLC murine models. CONCLUSION: Together, our study highlight the synthetic lethal relationship between Keap1 and PHF10, and provide targeting PHF10-SMARCA2 complex as an effective option to hit Keap1-deficient NSCLC.
Longitudinal Circulating Tumor DNA Profiling as a Biomarker for Response and Resistance in Platinum-Refractory Head and Neck Squamous Cell Carcinoma.
Choi W, Lee JH, Ryu J … +8 more , Choi SW, Jung YS, Park JY, Ryu CH, Choi SY, Park WS, Kong SY, Yun T
Cancer Res Treat · 2025 Nov · PMID 41197526 · Publisher ↗
PURPOSE: Immune checkpoint inhibitors (ICIs) are the standard treatment for platinum-refractory head and neck squamous cell carcinoma (HNSCC). This study aimed to characterize genomic alterations, monitor dynamic changes...
PURPOSE: Immune checkpoint inhibitors (ICIs) are the standard treatment for platinum-refractory head and neck squamous cell carcinoma (HNSCC). This study aimed to characterize genomic alterations, monitor dynamic changes in circulating tumor DNA (ctDNA) associated with treatment response, and identify novel alterations linked to resistance through serial ctDNA profiling. MATERIALS AND METHODS: Patients with platinum-refractory HNSCC receiving nivolumab were enrolled. ctDNA was analyzed using FoundationOne Liquid CDx at baseline, 6 weeks after treatment, and at disease progression. RESULTS: A total of 36 patients were enrolled, and 33 were evaluable for ctDNA. The most frequent baseline alterations were TP53 (75.8%), followed by TERT (27.3%), NOTCH1 (24.2%), CDKN2A (12.1%), and CCND1 (12.1%). Of 27 patients with measurable lesions, 5 achieved a partial response with a response rate of 18.5%. Dynamic ctDNA profiling revealed all responders had marked reductions in both the sum of variant allele frequencies (sumVAF) and the maximum variant allele frequencies (maxVAF) across detected mutations. A decrease in sumVAF or maxVAF correlated with longer treatment durations, and patients with a >50% decrease in either sumVAF or maxVAF showed significantly longer progression-free survival. Additionally, serial profiling identified de novo mutations in 17 patients, detected during stable disease or progression. CONCLUSION: Serial ctDNA analysis provides a noninvasive tool for monitoring treatment response and detecting emerging resistance in HNSCC treated with ICIs. A significant reduction in ctDNA at 6 weeks was associated with improved clinical outcomes and warrants validation in larger, prospective studies to define its role as a predictive biomarker in HNSCC.
Phase 1 Study of IMC-002, a Next-Generation Anti-CD47 Antibody, in Advanced Solid Tumors.
Ahn JS, Hong JY, Park JO … +8 more , Lee SY, Kim S, Yun HY, Ock CY, Hwang W, Kim SH, Kim HT, Lim HY
Cancer Res Treat · 2025 Nov · PMID 41197525 · Publisher ↗
PURPOSE: IMC-002 is a fully human cluster of differentiation 47-targeted immunoglobulin G4 monoclonal antibody, designed to minimize off-target effects. This study (NCT05276310) assessed its safety/tolerability and preli...
PURPOSE: IMC-002 is a fully human cluster of differentiation 47-targeted immunoglobulin G4 monoclonal antibody, designed to minimize off-target effects. This study (NCT05276310) assessed its safety/tolerability and preliminary anti-tumor activity in patients with advanced solid tumors who were not eligible for or had progressed on standard treatment. MATERIALS AND METHODS: Here we report results from the initial 3 + 3 design dose-escalation part of a two-part Phase 1, open-label, dose-escalation/expansion study. IMC-002 was administered intravenously every 2 weeks at four doses (5, 10, 20, and 30 mg/kg). The primary objective was to assess safety/tolerability, including maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). Secondary objectives included pharmacokinetics and clinical activity, including best overall response (BOR), disease control rate (DCR), and clinical benefit rate (CBR). RESULTS: Twelve patients were included in total, with three per dose level. Most patients (11/12) had stage IV disease; 7/12 had received three prior systemic therapies. No dose-limiting toxicities were observed and MTD was not reached. The most common treatment-related adverse events (TRAEs) were rash (9/12), vitreous floaters (8/12), and (hemolytic) anemia (5/12). There was no treatment-related thrombocytopenia, neutropenia, or infection. IMC-002 had dose-proportional pharmacokinetics, achieving steady state levels from Cycle 2. BOR was stable disease in six patients (DCR 50.0%). CBR was 33% (four patients maintaining disease control for ≥6 months). CONCLUSION: IMC-002 demonstrated favorable safety/tolerability at doses of 5-30 mg/kg every 2 weeks. RP2D was defined as 20 mg/kg every 3 weeks. Preliminary anti-tumor activity was observed, with a CBR of 33%.
Impact of Cell-of-Origin and MYC/BCL2 Status on the Risk of Central Nervous System Relapse in Primary Breast Diffuse Large B-Cell Lymphoma.
Lee CH, Song GY, Yhim HY … +17 more , Yoon DH, Jang KY, Yoon SE, Kim JS, Lee JO, Eom HS, Lee H, Kim KH, Kang KW, Do YR, Lee SI, Lee HS, Kim HJ, Ahn AR, Yang DH, Kim WS, Kwak JY
Cancer Res Treat · 2025 Nov · PMID 41197524 · Publisher ↗
PURPOSE: Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare entity with a distinct relapse pattern involving the central nervous system (CNS). However, data regarding predictors of CNS relapse in this populat...
PURPOSE: Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare entity with a distinct relapse pattern involving the central nervous system (CNS). However, data regarding predictors of CNS relapse in this population remain limited. MATERIALS AND METHODS: CNS relapse was retrospectively analyzed in two multicenter cohorts comprising 53 patients with newly diagnosed primary breast DLBCL, including a prospective trial and real-world cohort, all treated with rituximab-based immunochemotherapy. The impact of baseline clinical parameters, cell-of-origin, and MYC/BCL2 dual expression (DE) status on CNS relapse was assessed using a multivariate Cox regression model, separately conducted for the overall study set (n=53) and the immunohistochemical study set (n=36). RESULTS: By the CNS-International Prognostic Index (CNS-IPI), most patients were classified as low or intermediate risk; no patients were classified as high risk. With a median follow-up of 58.8 months, the 4-year risk of CNS relapse was 15.6% in the overall study set and 14.2% in the immunohistochemical set. MYC/BCL2 DE was identified in 14 patients (38.9%) and was significantly associated with increased risk of CNS relapse (4-year risk, 30.7% vs. 0%, p=0.001). Patients with non-germinal center B-cell-like subtype had a numerically higher risk of CNS relapse. However, in multivariate analysis, only MYC/BCL2 DE status was associated with CNS relapse. Synchronous bilateral involvement was also an independent predictor of CNS relapse in both study sets. CNS-IPI was not discriminatory for CNS relapse. CONCLUSION: MYC/BCL2 DE and synchronous bilateral breast involvement may help identify patients at higher risk for CNS relapse. Further studies are warranted.
Real World Efficacy and Safety of First Line Chemo Immunotherapy in Extensive Stage Small Cell Lung Cancer and its association with molecular subtype.
Han M, Park S, Lee SH … +5 more , Kim J, Kim JY, Sun JM, Ahn JS, Ahn MJ
Cancer Res Treat · 2025 Nov · PMID 41197523 · Publisher ↗
PURPOSE: Small cell lung cancer (SCLC) is an aggressive malignancy with poor outcomes. IMpower133 and CASPIAN established platinum-etoposide plus anti-PD-L1 antibody as standard first-line therapy for extensive-stage SCL...
PURPOSE: Small cell lung cancer (SCLC) is an aggressive malignancy with poor outcomes. IMpower133 and CASPIAN established platinum-etoposide plus anti-PD-L1 antibody as standard first-line therapy for extensive-stage SCLC (ES-SCLC). Real-world data in Korean patients are scarce. We evaluated the effectiveness and safety of first-line chemo-immunotherapy in ES-SCLC and compared outcomes with pivotal trials. MATERIALS AND METHODS: We retrospectively reviewed patients diagnosed with ES-SCLC between 2018 and 2021. Overall survival (OS), progression-free survival (PFS), and time to next treatment (TTNT) were analyzed using Kaplan-Meier methods. Multivariate Cox regression identified prognostic factors. Objective response rate (ORR) was assessed by RECIST v1.1, and histological subtypes evaluated. RESULTS: Among 177 patients, median age was 66 years (range, 42-91), with 63.8% aged ≥65; most were male (92.7%) and ECOG 0-1 (91.5%). Smoking history was present in 80.8%. Baseline brain and liver metastases occurred in 27.7% and 26%. Median follow-up was 27.2 months (range, 3.9-43.2). ORR was 74.5% (95% CI, 67.1-81.1). Median OS, PFS, and TTNT were 12.4 (95% CI, 11.6-14.9), 5.3 (95% CI, 5.1-5.87), and 5.6 months (95% CI, 1.43-38.27). In 49 patients with brain metastases, ORR was 63.2%, with no difference in efficacy. Local therapy for brain metastases improved OS (HR 0.42; p=0.012), while PFS was not different. Treatment-related adverse events occurred in 90%, primarily grade ≥2 cytopenias; the most common immune-related event was grade 1 rash. CONCLUSION: In this real-world Korean cohort, first-line chemo-immunotherapy achieved outcomes comparable to pivotal trials, supporting its role as standard care for ES-SCLC in clinical practice.
The Impact of Post Mastectomy Radiotherapy on T1-2N0-1 Male Breast Cancer and establishment of an artificial neural network predicting model: Population-Based Study.
Huang K, Yu Y, Li X … +4 more , Liu Y, Huang K, Wang X, Zhang J
Cancer Res Treat · 2025 Nov · PMID 41197522 · Publisher ↗
PURPOSE: The objective of this study was to analyze the impact of post-mastectomy radiotherapy (PMRT) in male breast cancer (MBC) patients and develop an artificial neural network (ANN) model to identify a potential PMRT...
PURPOSE: The objective of this study was to analyze the impact of post-mastectomy radiotherapy (PMRT) in male breast cancer (MBC) patients and develop an artificial neural network (ANN) model to identify a potential PMRT benefit population. MATERIALS AND METHODS: Data from a total of 2,247 MBC patients with T1-2N0-1M0 who underwent total mastectomy between 1998 and 2016 were enrolled from the SEER database. Propensity score matching was used to reduce covariate imbalances. Cox regression analysis was conducted to compare overall survival (OS) between the PMRT and no-PMRT groups. The hypothesis was that patients who had undergone PMRT and lived longer than the median OS of the no-PMRT group could benefit from PMRT. An ANN model was then developed to predict PMRT benefit population. RESULTS: Multivariate Cox regression analysis demonstrated better OS in the PMRT group compared to the no-PMRT group of matched patients. This survival benefit was particularly significant in patients with grade III or T2N0 and T2N1 disease, while no significant difference was observed in patients with grade I/II or T1N0 and T1N1 disease. An ANN model was established to predict PMRT benefit population based on patients with T2N0/T2N1. The optimal cut-off value for the model predicted probability was 0.51. Survival curves indicated that a score of 0.51 could accurately distinguish potential PMRT benefit population. CONCLUSION: For MBC patients with T2N0, T2N1, and grade III, PMRT would improve survival. The ANN model would be used to identify patients who are likely to benefit from PMRT and aid in clinical decision-making.
Predictive Role of Baseline Peripheral Lung SUVmax on PET/CT for Immune-Related Pneumonitis and Adverse Events in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors.
Kim KH, Kim SM, Lee JE … +3 more , Kim SS, Kang DH, Chung C
Cancer Res Treat · 2025 Oct · PMID 41166927 · Publisher ↗
PURPOSE: Immune checkpoint inhibitors (ICIs) offer durable responses in lung cancer patients lacking actionable mutations or with resistance to prior therapies. However, predicting their efficacy and associated immune-re...
PURPOSE: Immune checkpoint inhibitors (ICIs) offer durable responses in lung cancer patients lacking actionable mutations or with resistance to prior therapies. However, predicting their efficacy and associated immune-related adverse events (irAEs), such as severe pneumonitis, remains a clinical challenge. This study investigated the predictive value of positron emission tomography/computed tomography (PET/CT)-derived metabolic parameters for pneumonitis and other irAEs in lung cancer patients treated with ICIs. MATERIALS AND METHODS: We retrospectively analyzed 151 patients with advanced non-small cell lung cancer (NSCLC) who received ICIs as first-line treatment, either as monotherapy or in combination. Pre-treatment PET/CT was used to measure SUVmax at the primary tumor, tumor-uninvolved peripheral lung, and metastatic sites. Pneumonitis and irAEs were assessed using clinical and radiological findings. RESULTS: Pneumonitis, severe pneumonitis (grade ≥3), and irAEs occurred in 26.5%, 19.9%, and 37.1% of patients, respectively. A peripheral SUVmax cutoff of >1.1 significantly predicted pneumonitis (area under the curve [AUC] = 0.720, p <0.001). High peripheral SUVmax was associated with higher rates of pneumonitis (42.9% vs. 12.3%, p <0.001), severe pneumonitis (31.4% vs. 9.9%, p=0.001), and irAEs (46.4% vs. 29.5%, p=0.038). In multivariate analysis, high peripheral SUVmax independently predicted pneumonitis (odds ratio [OR]: 4.621; 95% confidence interval [CI]: 1.868-11.431; p=0.001), severe pneumonitis (OR: 2.848; 95% CI: 1.043-7.779; p=0.041), and irAEs (OR: 2.509; 95% CI: 1.114-5.504; p=0.022). CONCLUSION: Baseline peripheral SUVmax on PET/CT may serve as a noninvasive biomarker for predicting immune-related pneumonitis and other irAEs in NSCLC patients receiving ICIs, supporting early risk identification.
Chemoradiotherapy Increases the Incidence Rate of Cachexia in Head and Neck Cancer: A Cohort Study.
Lin NC, Sun KT, Tseng YH … +2 more , Shieh TM, Shih YH
Cancer Res Treat · 2025 Oct · PMID 41166926 · Publisher ↗
PURPOSE: In Taiwan, head and neck cancer (HNC) ranks among the five most prevalent cancers in men. HNC tumours can impair the patient's ability to ingest food following treatment, which may lead to cachexia. Currently, i...
PURPOSE: In Taiwan, head and neck cancer (HNC) ranks among the five most prevalent cancers in men. HNC tumours can impair the patient's ability to ingest food following treatment, which may lead to cachexia. Currently, in Taiwan, no study has investigated the association between the risk of cachexia and the patients' clinical characteristics. MATERIALS AND METHODS: This retrospective cohort study analysed data from the cancer registry database of Show-Chwan Memorial Hospital between 2021-2022. We evaluated 115 patients who underwent initial treatment and assessed the presence of cachexia 6 months after treatment. Clinical data were collected and compared between patients with cachexia and those without cachexia to explore the associated risk factors in the HNC population. RESULTS: In the database, oral cancer constituted the primary diagnosis for 70% of cases. According to pathological assessments, most patients presented with locally advanced disease and moderate tumour differentiation. No correlation was observed between patient-reported complications, risk behaviours, and the incidence of cachexia. Notably, patients who underwent concurrent chemoradiotherapy exhibited a 3.8-fold higher risk of developing cachexia. CONCLUSION: Concurrent chemotherapy is the leading risk factor of treatment-induced cachexia. The results of this study could help clinicians manage this issue adequately and devise solutions to limit its incidence.
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