Oncology最新文献

The article "Post-Progression Treatments after Palbociclib plus Endocrine Therapy in HR+/HER2- Metastatic Breast Cancer Patients: What Is the Better Choice?" [Oncology 2021; https://doi.org/10.1159/000521252] by Alessandra Fabi, Mariangela Ciccarese, Sinome Scagnoli, Michelangelo Russillo, Francesco Schettini, Giuseppe Buono, Vito Lorusso, Katia Cannita, Grazia Arpino, Simonetta Stani, Michela Palleschi, Rosalba Rossello, Giuseppina Sarobba, Agnese Fabbri, Marianna Giampaglia, Patrizia Pellegrini, Vincenzo Adamo, Francesca Morelli, Vittoria Barberi, Gianluigi Ferretti, Giovanna Catania, Simona Pisegna, Francesco Cognetti and Diana Giannarelli has been retracted by the Publisher and the Editor.After peer review, the accepted, unedited manuscript was published online as Early View. The authors did not respond to our requests and communication regarding the production process of their article despite extensive attempts at contact. As the article has not been approved by the authors for publication, we cannot publish the final version. To avoid confusion for readers we are retracting the Early View accepted, unedited manuscript.The authors did not respond to correspondence about the retraction.

Introduction: Nivolumab has become an essential therapeutic agent for patients with advanced or recurrent gastric cancer. However, the impact of metastatic patterns on its clinical efficacy has not been fully elucidated. This study aimed to clarify the association between distinct metastatic patterns and outcomes of nivolumab monotherapy.

Methods: Ninety-two patients with advanced or recurrent gastric cancer who received nivolumab were retrospectively analyzed. Clinicopathological variables, including performance status, HER2 expression, and predominant metastatic pattern, were correlated with survival outcomes and response rates.

Results: The median observation period was 48.3 months. The median overall (OS) and progression-free (PFS) survival for the entire cohort were 5.80 and 2.43 months, respectively. Patients with ECOG performance status 2-3 had significantly shorter survival than those with PS 0-1. HER2-positive status was associated with longer PFS. When stratified by metastatic pattern, the lymph node metastasis group showed markedly longer survival (median OS 35.1 months, PFS 11.9 months) than the peritoneal (OS 4.66, PFS 2.36 months) and hematogenous/other groups (OS 5.80, PFS 2.10 months). The objective response and disease control rates were also significantly higher in the lymph node group.

Conclusion: The pattern of metastatic spread, particularly lymphatic involvement, appears to influence the efficacy of nivolumab in advanced or recurrent gastric cancer. Recognizing metastatic patterns may assist in optimizing patient selection and therapeutic strategies for immune checkpoint blockade.

Introduction: The regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) remains the standard first-line treatment for diffuse large B-cell lymphoma (DLBCL), yet many patients relapse. Polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) has shown promise in trials. This study investigates the real-world efficacy and safety of Pola-R-CHP versus R-CHOP.

Methods: We retrospectively analyzed 505 DLBCL patients treated at Peking Union Medical College Hospital between January 2011 and March 2025. Thirty-six patients received Pola-R-CHP; 36 matched R-CHOP patients were selected using 1:1 propensity score matching based on age, sex, subtype, stage, and IPI. Outcomes included interim and end-of-treatment response, overall survival (OS), progression-free survival (PFS), and adverse events (AEs).

Results: Post-matching, 72 patients were included. Pola-R-CHP achieved higher interim complete response (CR) (72.2% vs. 63.9%, p = 0.035) and objective response rate (ORR) (100.0% vs. 83.3%, p = 0.011). At the end of treatment, CR was further improved (88.9% vs. 63.9%, p = 0.007), and ORR remained superior (100.0% vs. 86.1%, p = 0.020). At a median follow-up of 13.3 months (range, 1.1-141.9 months), 1 death and 2 progressions occurred in the Pola-R-CHP group compared with 9 deaths and 9 progressions in the R-CHOP group. Median OS and PFS were not reached in either cohort. At 12 months, the estimated OS was 97% for Pola-R-CHP and 94% for R-CHOP (p = 0.825), while the estimated PFS was 86% and 94%, respectively. This represented a numerical but not statistically significant difference (p = 0.457), likely reflecting the immature survival data and limited number of events at the time of analysis, rather than a true efficacy difference. Neutropenia was the most frequent AE (69.4%) and showed comparable severity between groups, while grades ≥3 AEs were numerically less frequent with Pola-R-CHP (8.3% vs. 13.9%, p = 0.453).

Conclusion: Pola-R-CHP achieved higher interim and end-of-treatment response rates than R-CHOP with a comparable safety profile. However, survival outcomes remain immature, and given the small matched sample size (n = 72), these findings should be interpreted cautiously and confirmed in larger prospective studies.

Introduction: Hyperthermic intrathoracic chemotherapy (HITHOC) is an intraoperative treatment that involves the perfusion of heated chemotherapy agents within the thoracic cavity. Photodynamic therapy (PDT) utilizes systemically administered photosensitizing agents and targeted light exposure to eliminate residual cancer cells during the surgery. This study aimed to present our experience with local therapies in the management of pleural malignancies, describe the respective outcomes of each modality, and make a preliminary comparison.

Methods: We retrospectively and consecutively enrolled patients with advanced intrathoracic cancer (lung cancer, mesothelioma, and thymoma) with pleural involvement who underwent surgical resection followed by HITHOC or PDT at a single medical center between June 2005 and December 2022. Patients with extrathoracic metastases were excluded. The primary outcomes assessed were mortality rates and overall survival (OS), while the secondary outcomes included recurrence rates and progression-free survival (PFS).

Results: Seventy patients were included, with 15 undergoing HITHOC and 55 undergoing PDT. No significant differences were observed in terms of age, gender, or pathological stage between the two groups. Perioperative parameters, including operative time, estimated blood loss, postoperative length of stay, and intensive care unit stay duration, did not differ significantly between groups. Among patients with recurrence, 50% had localized disease within the chest cavity. HITHOC showed a 3-year OS of 70.5% and 2-year PFS of 46.8% (median follow-up 18.33 months), while PDT showed a 5-year OS of 53.4% and 5-year PFS of 25.5% (median follow-up 73.07 months).

Conclusions: The clinical outcomes of our cohort are comparable to previous studies. Our preliminary data also suggest that HITHOC and PDT may have similar efficacy in treating pleural malignancies. However, the long-term outcomes associated with different neoadjuvant and adjuvant therapies remain unidentified.

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.