Oncology最新文献

Introduction: Lung cancer prevalence is rising in Taiwan, with female gender and family history being key factors. This study evaluated the predictive capabilities of the PGS000070 polygenic risk score (PRS) model in Taiwanese populations, analyzing patient outcomes, pathology type, comorbidities, smoking history, and surgical procedures.

Methods: A retrospective analysis using data from 54,962 participants in the Taiwan Precision Medicine Initiative. Among them, 1,673 participants with lung cancer were genotyped using the Affymetrix Genome-Wide TWB 2.0 SNP array. Logistic regression explored the association between PGS000070 and lung cancer risk in both genders. Subgroup analysis was conducted for females.

Results: Among 1,673 individuals with complete genotypes, no significant age differences were observed among groups (p = 0.4157). Higher PGS000070 scores were significantly linked to elevated lung cancer risk. Females in the highest PRS quartile (Q4) had an odds ratio of 2.017 (95% confidence interval = 1.654-2.459, p < 0.0001) compared to the lowest quartile (Q1). Males showed a similar pattern. Lobectomy was most common in Q4 (25.12%), with higher lymph node dissection rates in Q4 (35.45%) compared to Q1 (27.51%).

Conclusion: This study demonstrates a significant association between PGS000070 and increased lung cancer risk in both genders. Higher PRS scores were linked to a higher proportion of surgeries. Prospective large-scale studies are needed to further investigate the interplay of sex, genetic background, and comorbidities.

Introduction: Eosinophil peroxidase (EPO) and myeloperoxidase (MPO) are large, cationic enzymes secreted by granulocytes that bind preferentially to negatively charged cancer cell membranes generated by Warburg metabolism. In the presence of halide cofactors and hydrogen peroxide (H₂O₂), and under acidic conditions that potentiate catalysis, they generate singlet oxygen (1O₂*), a metastable oxygen state with a microsecond lifetime and hundred nanometer-scale diffusion radius. This confines cytotoxicity to enzyme-bound surfaces, producing a spatially restricted therapeutic effect.

Methods: Human bladder cancer cell lines (5637, T24) and normal urothelial cells (SV-HUC1) were treated with porcine EPO or porcine MPO aggregate formulations in acidic medium (pH 5.3). Activation occurred when 10 millimolar (mM) H₂O₂ was added immediately prior to cell contact. Viability was assessed by MTS assay, and IC₅₀ values were determined by nonlinear regression. Mixed cultures of GFP+ SV-HUC1 and mCherry+ malignant cells were analyzed by fluorescence microscopy and flow cytometry. MPO binding was assessed by immunofluorescence, and DNA damage was evaluated by Western blotting for γH2AX and phospho-ATM. Independent toxicity of individual components was also tested.

Results: Aggregate formulations selectively eliminated bladder cancer cells while sparing SV-HUC1. IC₅₀ values were in the nanomolar haloperoxidase range for malignant cells, with SV-HUC1 remaining viable at concentrations up to 200 nM. In mixed cultures, malignant cells were preferentially eliminated, while GFP+ SV-HUC1 remained intact. Immunofluorescence confirmed MPO binding to malignant membranes, and DNA damage markers were induced only in cancer cells. Component testing showed no cytotoxicity from enzymes, cofactors, or 10 mM H₂O₂ alone; only higher peroxide concentrations produced injury.

Conclusion: Selective cytotoxicity arises from concurrent enzyme binding and 1O₂* generation in mild acidic conditions rather than from direct peroxide toxicity. Haloperoxidase therapy thus offers a precise, contact-driven approach for post-bulk tumor treatment in non-muscle invasive bladder cancer.

Background: Pancreatic adenocarcinoma (PDAC) is a disease process that carries high morbidity and mortality and is suspected to supplant colorectal cancer as the second leading cause of cancer-related death in the USA. Resectable disease is considered no tumor contact with the celiac axis, common hepatic artery, or superior mesenteric artery and less than 180-degrees contact with portal vein or superior mesenteric vein. The current standard of care for resectable disease is surgery.

Summary: There is an ongoing paradigm shift to consider neoadjuvant therapy (NAT) for initially resectable disease and this review aims to summarize the updates in NAT for resectable pancreatic cancer. We performed a literature search of NAT for resectable PDAC and reviewed pertinent literature for current treatment regimens, clinical trials comparing NAT to up-front resection, and other modalities in the treatment of PDAC.

Key messages: Retrospective studies, recent completed prospective studies, and ongoing trials are showing an increased consideration for NAT for resectable PDAC compared with up-front surgery. Additionally, immunotherapy, cell therapy, and matrix-depleting therapy are promising new avenues in the treatment of pancreatic cancers.

Introduction: B-cell maturation antigen-targeting bispecific antibodies such as teclistamab have been associated with increased risk of infections as compared with conventional treatment regimens. This study explored the efficacy of intravenous immunoglobulin (IVIG) prophylaxis in reducing infection-related hospitalizations (IRHs) in MM patients who underwent treatment with teclistamab.

Methods: This was a retrospective study of MM treated with teclistamab at Taussig Cancer Center from December 16, 2022, to March 31, 2024. The primary endpoint was incidence rate of IRHs per patient-day on-IVIG vs. off-IVIG.

Results: Among the 44 patients included in the study, there were 19 infectious episodes that required inpatient hospitalization, occurring among 17 patients. Five infections occurred during 4,378 days during the "on-IVIG" period, compared to 14 infections occurring during 4,619 days for the "off-IVIG" period for an infectious incidence rate ratio between the two groups of 2.65 (p value = 0.027).

Conclusion: Patients treated with bispecific antibodies such as teclistamab are highly susceptible to infections due to impaired humoral immunity and hypogammaglobulinemia. Our findings demonstrate a reduction in infection incidence in patients while receiving IVIG. These results support the use of IVIG as an effective prophylactic strategy to reduce infectious risk in this vulnerable patient population.

Introduction: Abemaciclib (ABE) is a selective cyclin-dependent kinase 4/6 inhibitor widely used in breast cancer treatment. ABE inhibits renal tubular transporters, such as organic cation transporter 2, multidrug and toxin extrusion protein (MATE) 1, and MATE2-K, thereby suppressing creatinine excretion. This leads to a reversible increase in serum creatinine (Scr) without causing true renal injury. Since Scr is commonly used to assess renal function and guide medication dose adjustments, this effect may influence the management of concomitant renally excreted drugs. We aimed to evaluate the impact of ABE-induced Scr changes on the dosing of concomitant renally excreted medications in real-world clinical practice.

Methods: In this retrospective observational study, we included female patients who initiated ABE at Hokkaido Cancer Center between March 1, 2018, and March 31, 2023. Renal function was classified based on the Kidney Disease: Improving Global Outcomes guidelines, using creatinine clearance (CCr) cutoff values of 60 mL/min and 30 mL/min. The primary endpoint was the proportion of patients whose renal function classification changed post-ABE initiation, based on the lowest CCr value recorded during treatment.

Results: Of 221 patients included in this study, 30.8% had grade ≥2 Scr elevation at 1 month post-ABE initiation, increasing to 56.6% after 2 years. CCr significantly decreased after ABE initiation compared with that at baseline (median [interquartile range]: 44.5 [34.7-55.7] mL/min vs. 61.6 [49.3-81.1] mL/min, p < 0.01). After ABE discontinuation, CCr values returned to baseline levels. Overall, 50.2% of patients experienced a change in renal function classification after ABE initiation (p < 0.01), and 22.6% required dose adjustment owing to these changes.

Conclusion: ABE administration led to Scr elevation and changes in renal function classification in approximately half of patients, impacting dose adjustment of concomitant renally excreted medications. Therefore, appropriate management methods, including cystatin C-based renal evaluation, are necessary.

Background: This is a perspective article with the aim to contextualize Halberstaedter's legacy and outline lessons for modern oncology, rather than to exhaustively review all literature. We revisit Prof. Ludwig Halberstaedter's 1928 report on the Radiology Institute at Charité Hospital in Berlin, Germany, marking its 25th anniversary with added historical and scientific context.

Summary: The Radiology Institute (Roentgenabteilung) was established in 1916. This article illuminates the history of modern radiotherapy. Motivated by the upcoming centennial of his contributions, we performed a detailed historical and document analysis of his original article, contextualizing his methods and clinical observations within early twentieth century oncology and comparing them to today's challenges. This reflective article aimed to contextualize Halberstaedter's legacy and outline lessons for modern oncology, rather than exhaustively reviewing all literature. Halberstaedter's work chronicles the technical challenges of early X-ray and radium equipment, his pioneering use of fractionated high-voltage irradiation, and the strategic integration of radiotherapy with surgery and adjuvant radium applications. He championed standardized dosage protocols, quality control measures, and patient selection criteria to minimize morbidity. These developments have marked significant progress in cancer care, with growing attention to reducing morbidity and enhancing patient quality of life. He championed optimization of radium carriers for postoperative tumor cavities, experimented with intratumoral radiosensitizers, and collaborated across disciplines to refine treatment. He claimed that these innovations improved local control and patient quality of life despite the limited systemic therapies of the era. Engaging with Halberstaedter's report underscored several personal lessons: the critical importance of technological advancement and standardization, the value of interdisciplinary collaboration, and the need for patient-centered care. It also highlights how early empirical experiments, even when unsuccessful, laid the conceptual groundwork for targeted and multimodal therapies.

Key messages: Halberstaedter's visionary integration of scientific inquiry with compassionate clinical practice not only established foundational radiotherapy principles but also continues to inspire contemporary precision oncology and the ongoing pursuit of personalized, quality-driven cancer care.

Introduction: The prognosis of patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer (EGFR-m-NSCLC) has improved with the introduction of oral EGFR- tyrosine kinase inhibitor (TKI). Lower adherence to oral anticancer medications is reportedly associated with a poor prognosis. It is important to understand the causes of lower adherence to oral anticancer medications. We aimed to assess the potential risk factors associated with low adherence to EGFR-TKIs in a real-world clinical setting using administrative claims data in Japan.

Methods: We identified 10,809 outpatients routinely prescribed EGFR-TKIs between December 2015 and January 2023. Adherence to EGFR-TKIs was assessed based on the medication possession ratio (MPR) during the 12-month follow-up period from the date of first outpatient EGFR-TKI prescription. Multivariable linear regression analysis was performed to identify the potential risk factors associated with lower adherence.

Results: The mean (standard deviation) MPR was 94.1% (14.0). Lower adherence was associated with increasing age (per 10-year increase), female sex, dysphagia, and a higher number of concomitant oral medications (per doubling of the count).

Conclusion: Adherence to EGFR-TKIs was generally high, but the findings support tailored adherence strategies, especially for older patients and for those with a higher number of concomitant oral medications, including medication review to reduce pill burden and proactive support for swallowing difficulties.

Introduction: Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have transformed the management of ALK-rearranged non-small-cell lung cancer (NSCLC), yet their cardiotoxicity profile remains incompletely characterized, particularly with respect to sex differences. Given the high prevalence of cardiovascular disease in patients with NSCLC, understanding potential sex-specific risks is critical.

Methods: We conducted a pharmacovigilance analysis using the US FDA Adverse Event Reporting System (FAERS) database (Q1 2004-Q3 2021) to examine cardiotoxicity signals associated with five ALK-TKIs (alectinib, brigatinib, ceritinib, crizotinib, and lorlatinib). Adverse events were classified using the MedDRA hierarchy, focusing on cardiac disorders. Disproportionality analysis was performed via the Bayesian Confidence Propagation Neural Network (BCPNN) method, calculating Information Component (IC) scores. Sex differences were assessed by computing the IC delta and its 95% confidence interval.

Results: Cardiotoxicity signals, particularly heart failure and pericardial disorders, were detected for alectinib, ceritinib, crizotinib, and lorlatinib but not brigatinib. Notably, significant female-specific signals emerged for left ventricular failure with alectinib; pericardial disorders with ceritinib and crizotinib; and heart failure not elsewhere classified (the MedDRA category used for heart failure cases that do not fall into specific classifications) with crizotinib.

Conclusion: This is the first study to identify sex differences in ALK-TKI-associated cardiotoxicity, highlighting a consistent female predominance in reported adverse events. In particular, considering its widespread use and the clinical importance of left ventricular failure, the pronounced disproportionality signal of cardiotoxicity in females associated with alectinib is thought to have substantial clinical impact. These results underscore the need for heightened clinical vigilance and further research into sex-specific risk stratification and preventive strategies for cardiotoxicity in patients receiving ALK-TKIs.

Introduction: Palbociclib and abemaciclib, CDK4/6 inhibitors with a shared primary mechanism of action, differ in their adverse effect profiles. We encountered several cases of switching between CDK4/6 inhibitors following treatment discontinuation owing to adverse events (AEs) in clinical practice.

Methods: In this study, we evaluated the safety and treatment continuity of switching between palbociclib and abemaciclib for hormone receptor-positive HER2-negative metastatic or recurrent breast cancer (HR+/HER2-MBC) in patients and prescribed these agents between January 1, 2018, and August 31, 2024, at Ogaki Municipal Hospital. Patients who did not discontinue treatment owing to AEs were defined as the non-AE group (79 patients), those who switched to another CDK4/6 inhibitor after treatment discontinuation owing to AEs were defined as the AE-switch group (16 patients), and those who did not switch to another CDK4/6 inhibitor after treatment discontinuation owing to AEs were defined as the AE-stop group (13 patients).

Results: The main AEs for which treatment was discontinued included neutropenia, interstitial lung disease, increased AST and ALT levels, gastrointestinal symptoms, and skin disorders. Switching only caused recurrent neutropenia, with no serious recurrence being observed for the other AEs. The median progression-free survival in the non-AE, AE-switch, and AE-stop groups was 392, 1,043, and 203 days (p = 0.00858), and the median overall survival was 1,598, 3,725, and 1,701 days (p = 0.269), respectively.

Conclusion: These results suggest that switching following the emergence of AEs may be useful in terms of safety and treatment continuity of CDK4/6 inhibitor therapy for HR+/HER2-MBC. However, since this study was an exploratory analysis based on real-world data from a single center in Japan, further validation through large-scale, prospective, multicenter clinical trials is warranted.

Introduction: The burden of androgen deprivation therapy (ADT) is only partially captured by legacy prostate cancer questionnaires, which devote few items to hormonal sequelae. Patient-Reported Evaluation of the Effects of Hormone Therapy (PREVES-HOR) is a 29-item, distress-anchored instrument developed to quantify ADT-specific physical, emotional, cognitive, sexual, and body image morbidity from a patient-centered, subjective perspective. We report the prespecified phase 1 psychometric evaluation.

Methods: Italian-speaking men receiving ADT were consecutively enrolled. Participants completed PREVES-HOR plus external comparators for fatigue (REST), mood (HEAL-BDLC), sleep (PEACE), and well-being (WHO-5). Internal consistency was estimated with Cronbach's α and McDonald's ω; convergent validity with Spearman correlations; dimensionality with exploratory factor analysis (polychoric matrix, principal axis factoring, oblimin rotation, parallel analysis).

Results: One hundred and forty-five patients were analyzed. PREVES-HOR showed excellent reliability (α = 0.95; McDonald's ω = 0.97; domain α/ω 0.80-0.95). Six factors - physical fatigue and pain, emotional well-being, mental clarity, quality of life, relationships and stress, sexual health and body image - accounted for 79% of variance, with a dominant general distress factor (∼50%). All but four items had communalities ≥0.40 and cross-loadings <0.30. Total PREVES-HOR correlated strongly with fatigue (REST ρ = 0.69) and depression/anxiety (HEAL-BDLC ρ = 0.78) and inversely with well-being (WHO-5 ρ = -0.49) and sleep quality (PEACE ρ = -0.37), confirming convergent but nonredundant validity.

Conclusion: Phase 1 findings support PREVES-HOR's content validity, internal coherence, and ability to detect clinically meaningful distress overlooked by broader instruments such as EPIC or FACT-P. Its forced-choice format eliminated missing data but will be reconsidered, along with responsiveness, test-retest stability, and cross-cultural adaptation, in the ongoing 1,000 patient phase 2/3 program. Pending confirmation, PREVES-HOR, may become a complementary tool for individualizing supportive care and evaluating ADT-modifying interventions.