BACKGROUND:The novel RANO risk score provides prognostic stratification for patients with IDH-wildtype glioblastoma(GBM) and includes age, Karnofsky Performance Scale(KPS), RANO resection class(RRC), and MGMT promoter methylation(MGMTm). However, MGMTm testing is unavailable in many countries. We aimed to explore the prognostic performance of a RANO-adapted clinical score excluding MGMTm. METHODS:We applied the same scoring system established by original RANO score, excluding MGMTm. Three risk classes were defined as numerical scores derived through tertiles. The primary endpoint was overall survival(OS), and the secondary exploratory endpoint was progression-free survival(PFS). RESULTS:One-hundred twenty patients were included. Three risk classes were identified:low-risk(0-1 points,n:47, 39.2%), intermediate-risk(2-3 points,n:27, 22.5%), and high-risk(≥4 points,n:46, 38.3%). The median OS was 35.5 months(95% CI:21.1-49.9) for the low-risk group, 16 months(95% CI:9.9-22.1) for the intermediate-risk group, and 5 months(95% CI:3.6-6.3) for the high-risk group(p < 0.001). Similarly, the median PFS was 16.3 months(95% CI:12.3-20.3) for the low-risk group, 9.9 months(95% CI:7.2-12.6) for the intermediate-risk group, and 4.1 months(95% CI:3.5-4.7) for the high-risk group(p < 0.001). CONCLUSION:This simplified RANO-adapted score demonstrated promising prognostic stratification using basic clinical parameters. As a pragmatic adaptation study, external validation is required before clinical application, particularly in settings where MGMTm testing is unavailable.
AIMS:Patients with distant metastases of differentiated thyroid cancer (DM-DTC) exhibit significant heterogeneity in clinical characteristics and prognosis. This study aimed to investigate prognostic variables affecting overall survival (OS) in radioiodine-refractory (RAIR) patients and to predict the radioiodine therapy (RAIT) response and stimulated thyroglobulin (sTg) levels in non-radioiodine-refractory (NRAIR) patients. METHODS:A retrospective analysis was conducted on 146 patients of DM-DTC undergoing RAIT, categorizing them into an RAIR group (n = 56) and an NRAIR group (n = 90). Kaplan-Meier assessed survival, Cox regression identified RAIR prognostic factors, and logistic regression explored sTg-treatment response in NRAIR. RESULTS:The median follow-up period was 71 months (IQR: 24-132 months).In RAIR, brain metastasis (HR = 5.49, 95% CI: 1.46-20.66, p = 0.012) and other-site metastases (HR = 4.11, 95% CI: 1.06-15.85, p = 0.004) were independent poor prognostic factors. In NRAIR, sTg ≤ 75 ng/mL predicted favorable response (sensitivity 84.8%, specificity 78.9%). CONCLUSIONS:RAIR status significantly impacts DM-DTC prognosis. Brain metastases or other-site metastases are independent prognostic factors in RAIR patients, highlighting the need for stratified treatment. In NRAIR patients, preliminary data suggest that sTg ≤ 75 ng/mL predicts a favorable treatment response.
PURPOSE:This study aimed to clarify the incidence of anthracycline-induced cardiotoxicity (ACT) and identify its clinical and candidate genetic risk factors in Chinese early-stage breast cancer patients, so as to provide evidence for clinical risk assessment and individualized cardiac protection. METHODS:This study included 119 patients who received anthracycline-based chemotherapy. Cardiac function was assessed via echocardiography at baseline, post-chemotherapy, and at one-year follow-up. Five candidate SNPs (CBR3 rs1056892, GSTP1 rs1695, SLC28A3 rs7853758, ABCB1 rs1045642, ABCC2 rs8187710) were genotyped to analyze their association with ACT. RESULTS:The incidence of ACT was 15.1% (18/119). No significant association was found between any of the five genotyped SNPs and the development of ACT (all p > 0.05). Multivariate logistic regression analysis identified older age, higher cumulative anthracycline dose, and the use of HER2-targeted antibodies (trastuzumab/pertuzumab) as independent clinical risk factors for ACT. CONCLUSION:In Chinese early-stage breast cancer patients, ACT is significantly associated with clinical risk factors rather than the selected candidate genetic polymorphisms. These findings support targeted cardiac monitoring and optimized treatment strategies for high-risk patients to reduce the occurrence of anthracycline-related cardiac injury.
BACKGROUND:Prostate cancer poses a substantial threat to men's health. Previous studies have hinted at potential links between dietary components like lipids and saturated fatty acids (SFAs) and prostate cancer, yet the precise relationships remain elusive. METHODS:A multicenter case-control study was executed. A total of 120 pathologically confirmed prostate cancer patients and 60 age- and BMI-matched healthy male controls were enrolled. High performance liquid chromatography (HPLC) was employed to quantitatively analyze the levels of saturated, monounsaturated, and polyunsaturated fats in both prostate cancer tissues and adjacent tissues. Statistical analyses were conducted using SPSS version 23.0 software. RESULTS:Triglycerides (OR = 4.23, 95% CI: 2.15-8.32, p < 0.001) and saturated fatty acid/fatty acid ratio (OR = 3.89, 95% CI: 1.98-7.64, p < 0.001) were significantly associated with prostate cancer risk. Both indicators were positively correlated with continuous Gleason score (triglyceride: β = 0.710, OR = 2.89, 95% CI: 1.96-4.26, p < 0.001; saturated fatty acid/fatty acid: β = 0.645, OR = 2.57, 95% CI: 1.78-3.71, p < 0.001), and were significantly elevated in prostate cancer tissues compared with adjacent non-cancerous tissues. CONCLUSION:This study confirms the importance of triglycerides and saturated fatty acid/fatty acid ratio in prostate cancer progression, which could be used for diagnosis and prognosis. Reducing their levels may help prevent prostate cancer.
Tenosynovial giant cell tumors (TGCT) are rare, locally aggressive neoplasms causing pain, stiffness, swelling, limited range of motion, and joint degeneration, which can be debilitating. Therapeutic options include surgery or systemic therapy with colony-stimulating factor 1 receptor (CSF-1R) pathway inhibitors. However, many are not amenable to surgery or have high postsurgical recurrence rates. Available systemic therapies require long-term administration and can have burdensome side effects. Emactuzumab is a novel, potent, CSF-1R inhibiting monoclonal antibody with a unique mechanism of action targeting the receptor dimerization interface of the CSF-1R to reduce tumor-associated macrophages and inflammation within the TGCT microenvironment. It is the only short-course, intravenous therapy in development for TGCT. In a phase I study, emactuzumab resulted in robust and durable responses, and a manageable safety profile in patients with TGCT, supporting further research as a treatment option to address unmet need and improve quality of life in patients with TGCT. TANGENT is a randomized, double-blind, global, phase III study (NCT05417789) to investigate the safety and efficacy of intravenous emactuzumab versus placebo in patients with TGCT not amenable to surgery.Clinical trial registration: www.clinicaltrials.gov identifier is NCT05417789 initially registered on 1 June 2022.
INTRODUCTION:Pathological complete response (pCR) is a key prognostic indicator in breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC). Unimodal prediction models are limited, underscoring the need for multimodal machine learning approaches. METHODS:This retrospective study included 211 BC patients. A radiomics score (Radscore) was developed from multiparametric MRI, and integrated with clinical predictors using machine learning to build three models: clinical, radiomics, and a combined clinical-radiomics model. Their performance was systematically compared. RESULTS:The combined clinical-radiomics model significantly outperformed unimodal models, with an AUC of 0.937 in the training cohort and 0.853 in the validation cohort. Decision curve and calibration analyses suggested potential clinical utility and accuracy. CONCLUSION:The clinical-radiomics model accurately predicts pCR to NAC in BC, surpassing unimodal methods. Its dynamic nomogram aids in personalizing treatment decisions.
AIMS:To evaluate the prognostic significance of the Lung Immune Prognostic Index (LIPI) in patients with metastatic gastric cancer (mGC). PATIENTS AND METHODS:We retrospectively analyzed 177 patients with mGC. Patients were stratified into three groups (good, intermediate, and poor) based on the LIPI score, which was calculated using a derived neutrophil-to-lymphocyte ratio (dNLR) >3 and lactate dehydrogenase (LDH) >upper limit of normal (ULN). Survival outcomes were analyzed using Kaplan-Meier and Cox regression models. RESULTS:In univariate analyses, intermediate and poor LIPI, elevated dNLR and LDH, ECOG performance status ≥1, low albumin, and high CRP were significantly associated with overall survival. In multivariate analysis, poor LIPI remained an independent prognostic factor (HR: 3.43; 95% CI: 1.30-9.05; p = 0.013). ECOG performance status and C-reactive protein (CRP) were also independently associated with survival. Subgroup analysis showed a more pronounced prognostic impact of LIPI in Human Epidermal Growth Factor Receptor 2 (HER2)-negative patients. CONCLUSIONS:The LIPI is a simple, noninvasive, and inexpensive tool that provides strong prognostic information for patients with mGC, potentially aiding in better risk stratification in clinical practice.
AIMS:Describe trends in real-world BRCA and homologous recombination deficiency (HRD) testing rates among patients with advanced epithelial ovarian cancer (EOC). METHODS:In this US-nationwide electronic health record-derived deidentified database study, eligible adult patients diagnosed with OC on/after 1 January 2016 had stage III/IV EOC at diagnosis, and initiated 1L platinum-based chemotherapy (1 January 2017-30 June 2023 [index date]). Results were descriptive. RESULTS:Among 2135 patients, 66.0% received BRCA and/or HRD testing before the final 1L chemotherapy dose. BRCA/HRD testing was higher among patients receiving chemotherapy-bevacizumab (78.6%) versus chemotherapy alone (60.6%). BRCA/HRD testing rates increased from 2017 to 2023. BRCA/HRD testing rates were lower among patients who were older (aged ≥75 years), had stage IV disease at diagnosis, were Black/African American, had nonserous epithelial histology, had an Eastern Cooperative Oncology Group performance status score of ≥2, and had no evidence of cytoreductive surgery. CONCLUSIONS:Real-world BRCA/HRD testing rates increased from 2017 to 2023 among US patients with EOC. Subgroups often underserved in US healthcare settings had lower testing rates, possibly preventing some from receiving optimal treatments. Increasing provider education and support for biomarker testing and improving patient access may help reduce differences and improve treatment outcomes.
BACKGROUND:Frontline (1L) treatment for transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM) has shifted from triplet (e.g. bortezomib [V], lenalidomide [R], dexamethasone [d]) to quadruplet (e.g. daratumumab with VRd [DVRd]) regimens, based on improved efficacy demonstrated in pivotal trials. This real-world study compared progression-free survival (PFS) in TE patients with NDMM treated with DVRd plus DR or R maintenance (DVRd-DR/R) versus VRd plus R maintenance (VRd-R). METHODS:Adult TE patients with NDMM who initiated DVRd-DR/R or VRd-R between 1 January 2020 and 30 June 2022 were identified through a retrospective chart review at 10 US sites. PFS was assessed using Kaplan-Meier analyses and propensity score-weighted hazard ratios (HR) were estimated using Cox regression. RESULTS:Overall, 137 patients received DVRd-DR/R and 86 received VRd-R. Over a median follow-up of 26.7 and 39.8 months among the DVRd-DR/R and VRd-R cohorts, respectively, 11 (9.1%) and 32 (29.7%) patients experienced disease progression or death. Median PFS was not reached in either cohort. DVRd-DR/R versus VRd-R was associated with 63% lower risk of disease progression or death (weighted HR: 0.37, 95% confidence interval: 0.17-0.80, p = 0.006). CONCLUSION:Findings aligned with pivotal trials, demonstrating the significant PFS benefit of 1L DVRd over VRd and supporting its real-world use for TE NDMM.
BACKGROUND:Pembrolizumab, FDA-approved in July 2021, administered in combination with chemotherapy is the standard neoadjuvant treatment for high-risk, early-stage, triple-negative breast cancer (esTNBC) due to its efficacy in the KEYNOTE-522 trial. Identifying factors influencing clinical adoption is key to optimizing patient outcomes. This study explored physicians' perspectives on pembrolizumab use in the neoadjuvant and adjuvant settings, focusing on the treatment decision-making process for esTNBC. METHODS:Eight US Oncology Network physicians (6 medical oncologists, 2 breast surgeons) participated in a survey and virtual focus group. Survey responses were analyzed descriptively, and focus group discussion transcripts underwent inductive thematic analysis. RESULTS:Four themes emerged: widespread adoption of pembrolizumab as standard of care in esTNBC, rare nonuse due to contraindications, continued adjuvant use, and management of estrogen receptor (ER)-low/HER2- breast cancer similar to TNBC. CONCLUSIONS:The study highlights broad integration of pembrolizumab for esTNBC patients due to survival benefits and manageable safety profile. Nonuse was limited to contraindications, patient preferences, or due to surgery referrals without medical oncology input. To optimize patient outcomes, future efforts should focus on physician-patient communication, multidisciplinary care coordination, and surgeon education regarding neoadjuvant guidelines. Further guidance for optimal adjuvant treatment of patients without pathological complete response is necessary.
Background HER2-positive breast cancer (BC) is an aggressive subtype that affects approximately 15-25% of patients.Objective This study aimed to identify sociodemographic factors associated with mortality among patients with HER2-positive BC treated with trastuzumab under the Ricarte Soto Law (RSL) in Chile between 2015 and 2024.Methods A cross-sectional observational design was used, based on a national database including 4,920 patients who accessed treatment through the RSL. Bivariate and multivariate logistic regression models were applied to evaluate factors associated with mortality.Results Older age, public healthcare system, and residence outside the Metropolitan Region were associated with higher mortality. These findings suggest that disparities in outcomes persist despite financial coverage of high-cost therapies, indicating the influence of structural and geographic factors on cancer care.Conclusions: This study provides real-world evidence to inform policies aimed at reducing inequities in access and outcomes among patients with breast cancer in Chile.
AIM:To assess healthcare resource utilization (HRU) and costs among patients with metastatic pancreatic cancer (mPC). PATIENTS AND METHODS:Adult US patients with an mPC diagnosis based on index date 1 January 2020-31 December 2022 were identified in the Merative MarketScan database. All-cause healthcare visits and costs (USD) were estimated per-person-per-month (PPPM) for 1 year post-index period. First-line (1L) treatments (≤90 days post-index) were categorized as FOLFIRINOX (leucovorin, fluorouracil, irinotecan, oxaliplatin)-based, gemcitabine+paclitaxel-based, other, or none. RESULTS:Claims from 2318 patients with mPC were included: 68.6% (1589/2318) with commercial and 31.4% (729/2318) with Medicare. Mean total costs PPPM were $34,215 with commercial and $15,158 with Medicare. A total of 25.7% (409/1589) of commercially insured patients and 43.2% (315/729) of Medicare-insured patients did not receive 1L treatment. Median (interquartile range) cumulative length of stay was 0.8 days (0.1-2.4) with commercial insurance and 0.7 days (0.0-2.4) with Medicare. All-cause PPPM costs were higher for patients without 1L treatment than with 1L treatment in both insurance types, primarily driven by inpatient and outpatient visits. CONCLUSIONS:Patients with mPC experienced high economic burden, mostly attributable to inpatient and outpatient costs. The high rate of patients with mPC not receiving 1L treatment merits further exploration.
Clear cell sarcoma (CCS) is an ultra-rare sarcoma with no established standard systemic therapy of proven efficacy. Mesenchymal-epithelial transition factor (MET) overexpression drives CCS progression and serves as a promising therapeutic target. Vebreltinib is a highly selective MET inhibitor with potential therapeutic benefits for CCS. Additionally, given that MET and programmed cell death protein 1 (PD-1) are both downstream molecules of melanocyte transcription factor (MITF), combined MET and PD-1 inhibition may block the MITF pathway more effectively. Moreover, aberrant MET activation indirectly upregulates programmed death ligand 1 (PD-L1), causing immune escape and resistance to PD-1 inhibitors; MET inhibition may potentially reverse this resistance. Here, we describe the rationale and design of VEBrant, a multicenter, phase II study aimed to evaluate the efficacy and safety of vebreltinib combined with PD-1-based immunotherapy in advanced CCS. Thirty patients will be enrolled, with the treatment cohort receiving combination therapy of vebreltinib and PD-1 inhibitor, and a reference cohort receiving physician's choice therapy or best supportive care. Primary endpoint is Objective Response Rate (ORR) by Simon two-stage design. This study will provide evidence for vebreltinib combined with PD-1-based immunotherapy and improve understanding of advanced CCS management.Clinical trial registration: www.clinicaltrials.gov identifier is NCT07153887.
INTRODUCTION:Second-generation covalent Bruton tyrosine kinase inhibitors (cBTKi), acalabrutinib and zanubrutinib, are standard-of-care for treatment-naïve adults with chronic lymphocytic leukemia (CLL). However, real-world evidence remains limited. METHODS:This real-world analysis compared acalabrutinib and zanubrutinib using the IntegraConnect PrecisionQ de-identified electronic health record database, representing >3 million cancer patients across 500+ US sites. Patients initiated cBTKi between January 2020 and November 2023, with follow-up through 3 July 2024. RESULTS:This study included 473 patients; 184 zanubrutinib-treated patients matched to 289 acalabrutinib-treated patients by age and sex. Baseline characteristics were similar. Median time to discontinuation (TTD) for acalabrutinib was 29.5 months (95% confidence interval [CI] 21.2, not reached [NR]). Median TTD for zanubrutinib was NR, with significantly longer duration of treatment than acalabrutinib (adjusted hazard ratio [aHR]: 0.50, 95% CI 0.3-0.7; p < .01). The 12-month probability of remaining on treatment with zanubrutinib (83.3%) was higher than acalabrutinib (69.5%). Toxicity-related discontinuation was higher with acalabrutinib (10.7%) than zanubrutinib (5.4%). Median time to next treatment was 42.5 months for acalabrutinib (95% CI 33.2-NR) and NR for zanubrutinib (aHR 0.82; 95% CI 0.5-1.4). CONCLUSION:Zanubrutinib demonstrated longer treatment persistence and fewer discontinuations attributed to toxicity during chart abstraction than acalabrutinib in treatment-naïve CLL.
BACKGROUND:The androgen receptor (AR) is a potential biomarker in breast cancer (BC), but its predictive and prognostic value-especially regarding neoadjuvant chemotherapy (NAC) response-remains unclear. This study evaluates the relationship between pre-treatment AR expression and both therapeutic response and survival outcomes. METHODS:A retrospective multicenter cohort of 194 BC patients treated with NAC was analyzed. AR expression was assessed by immunohistochemistry on pretreatment core biopsy samples. Associations between AR expression and clinicopathologic variables, pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS) were statistically evaluated. RESULTS:AR expression was significantly associated with hormone receptor positivity and lower tumor grade. However, no significant relationship was found between AR expression and pCR in the overall cohort or within molecular subtypes. Although AR-positive patients exhibited longer OS in univariate analysis (p = 0.024), this association was not sustained in multivariate models. CONCLUSION:Although AR expression correlates with favorable clinicopathologic features in BC patients undergoing NAC, it is not an independent predictor of pathological response or long-term survival outcomes. A key limitation is the analysis of the entire cohort together; given the contrasting biological roles of AR across different molecular subtypes, future studies should evaluate TNBC and Luminal tumors separately.
