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International Journal of Pharmaceutics Jun 2024Postoperative distant metastasis and high recurrence rate causes a dilemma in treating triple-negative breast cancer (TNBC) owing to its unforeseeable invasion into...
Postoperative distant metastasis and high recurrence rate causes a dilemma in treating triple-negative breast cancer (TNBC) owing to its unforeseeable invasion into various organs or tissues. The wealth of nutrition provided by vascular may facilitate the proliferation and angiogenesis of cancer cells, which further enhance the rates of postoperative metastasis and recurrence. Chemotherapy, as a systemic postoperative adjuvant therapy, is generally applied to diminish recurrence and metastasis of TNBC. Herein, an halofuginone-silver nano thermosensitive hydrogel (HTPM&AgNPs-gel) was prepared via a physical swelling method. The in vitro anticancer efficacy of HTPM&AgNPs-gel was analyzed by investigating cell proliferation, migration, invasion, and angiogenesis capacity. Furthermore, the in vivo anti-cancer activity of HTPM&AgNPs-gel was further appraised through the tumor suppression, anti-metastatic, anti-angiogenic, and anti-inflammatory ability. The optimized HTPM&AgNPs-gel, a thermosensitive hydrogel, showed excellent properties, including syringeability, swelling behavior, and a sustained release effect without hemolysis. In addition, HTPM&AgNPs-gel was confirmed to effectively inhibit the proliferation, migration, invasion, and angiogenesis of MDA-MB-231 cells. An evaluation of the in vivo anti-tumor efficacy demonstrated that HTPM&AgNPs-gel showed a stronger tumor inhibition rate (68.17%) than did HTPM-gel or AgNPs-gel used alone and exhibited outstanding biocompatibility. Notably, HTPM&AgNPs-gel also inhibited lung metastasis induced by residual tumor tissue after surgery and further blocked angiogenesis-related inflammatory responses. Taken together, the suppression of inflammation by interdicting the blood vessels adjoining the tumor and inhibiting angiogenesis is a potential strategy to attenuate the recurrence and metastasis of TNBC. HTPM&AgNPs-gel is a promising anticancer agent for TNBC as a local postoperative treatment.
PubMed: 38917957
DOI: 10.1016/j.ijpharm.2024.124384 -
PloS One 2024Meningiomas, the most prevalent primary benign intracranial tumors, often exhibit complicated levels of adhesion to adjacent normal tissues, significantly influencing...
Meningiomas, the most prevalent primary benign intracranial tumors, often exhibit complicated levels of adhesion to adjacent normal tissues, significantly influencing resection and causing postoperative complications. Surgery remains the primary therapeutic approach, and when combined with adjuvant radiotherapy, it effectively controls residual tumors and reduces tumor recurrence when complete removal may cause a neurologic deficit. Previous studies have indicated that slip interface imaging (SII) techniques based on MR elastography (MRE) have promise as a method for sensitively determining the presence of tumor-brain adhesion. In this study, we developed and tested an improved algorithm for assessing tumor-brain adhesion, based on recognition of patterns in MRE-derived normalized octahedral shear strain (NOSS) images. The primary goal was to quantify the tumor interfaces at higher risk for adhesion, offering a precise and objective method to assess meningioma adhesions in 52 meningioma patients. We also investigated the predictive value of MRE-assessed tumor adhesion in meningioma recurrence. Our findings highlight the effectiveness of the improved SII technique in distinguishing the adhesion degrees, particularly complete adhesion. Statistical analysis revealed significant differences in adhesion percentages between complete and partial adherent tumors (p = 0.005), and complete and non-adherent tumors (p<0.001). The improved technique demonstrated superior discriminatory ability in identifying tumor adhesion patterns compared to the previously described algorithm, with an AUC of 0.86 vs. 0.72 for distinguishing complete adhesion from others (p = 0.037), and an AUC of 0.72 vs. 0.67 for non-adherent and others. Aggressive tumors exhibiting atypical features showed significantly higher adhesion percentages in recurrence group compared to non-recurrence group (p = 0.042). This study validates the efficacy of the improved SII technique in quantifying meningioma adhesions and demonstrates its potential to affect clinical decision-making. The reliability of the technique, coupled with potential to help predict meningioma recurrence, particularly in aggressive tumor subsets, highlights its promise in guiding treatment strategies.
Topics: Humans; Meningioma; Elasticity Imaging Techniques; Female; Middle Aged; Male; Meningeal Neoplasms; Aged; Adult; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Tissue Adhesions; Algorithms
PubMed: 38917107
DOI: 10.1371/journal.pone.0305247 -
Journal of Neuro-oncology Jun 2024To better define the role of surgery, we investigated survival and functional outcomes in patients with multiple brain metastases.
PURPOSE
To better define the role of surgery, we investigated survival and functional outcomes in patients with multiple brain metastases.
METHODS
Pertinent clinical and radiological data of 131 consecutive patients (156 surgeries) were analyzed retrospectively.
RESULTS
Surgical indications included mass effect (84.6%) and need for tissue acquisition (44.9%, for molecularly informed treatment: 10 patients). Major (i.e. CTCAE grade 3-5) neurological, surgical and medical complication were observed in 6 (3.8%), 12 (7.7%), and 12 (7.7%) surgical cases. Median preoperative and discharge KPS were 80% (IQF: 60-90%). Median overall survival (mOS) was 7.4 months. However, estimated 1 and 2 year overall survival rates were 35.6% and 25.1%, respectively. Survival was dismal (i.e. mOS ≤ 2.5 months) in patients who had no postoperative radio- and systemic therapy, or who incurred major complications. Multivariate analysis with all parameters significantly correlated with survival as univariate parameters revealed female sex, oligometastases, no major new/worsened neurological deficits, and postoperative radio- and systemic therapy as independent positive prognostic parameters. Univariate positive prognostic parameters also included histology (best survival in breast cancer patients) and less than median (0.28 cm) residual tumor load.
CONCLUSIONS
Surgery is a reasonable therapeutic option in many patients with multiple brain metastases. Operations should primarily aim at reducing mass effect thereby preserving the patients' functional health status which will allow for further local (radiation) and systemic therapy. Surgery for the acquisition of metastatic tissue (more recently for molecularly informed treatment) is another important surgical indication. Cytoreductive surgery may also carry a survival benefit by itself.
PubMed: 38916848
DOI: 10.1007/s11060-024-04739-7 -
Journal of Nanobiotechnology Jun 2024Photothermal therapy (PTT) is a promising cancer treatment method due to its ability to induce tumor-specific T cell responses and enhance therapeutic outcomes. However,...
Photothermal therapy (PTT) is a promising cancer treatment method due to its ability to induce tumor-specific T cell responses and enhance therapeutic outcomes. However, incomplete PTT can leave residual tumors that often lead to new metastases and decreased patient survival in clinical scenarios. This is primarily due to the release of ATP, a damage-associated molecular pattern that quickly transforms into the immunosuppressive metabolite adenosine by CD39, prevalent in the tumor microenvironment, thus promoting tumor immune evasion. This study presents a photothermal nanomedicine fabricated by electrostatic adsorption among the Fe-doped polydiaminopyridine (Fe-PDAP), indocyanine green (ICG), and CD39 inhibitor sodium polyoxotungstate (POM-1). The constructed Fe-PDAP@ICG@POM-1 (FIP) can induce tumor PTT and immunogenic cell death when exposed to a near-infrared laser. Significantly, it can inhibit the ATP-adenosine pathway by dual-directional immunometabolic regulation, resulting in increased ATP levels and decreased adenosine synthesis, which ultimately reverses the immunosuppressive microenvironment and increases the susceptibility of immune checkpoint blockade (aPD-1) therapy. With the aid of aPD-1, the dual-directional immunometabolic regulation strategy mediated by FIP can effectively suppress/eradicate primary and distant tumors and evoke long-term solid immunological memory. This study presents an immunometabolic control strategy to offer a salvage option for treating residual tumors following incomplete PTT.
Topics: Animals; Photothermal Therapy; Immunotherapy; Mice; Nanomedicine; Tumor Microenvironment; Cell Line, Tumor; Humans; Indocyanine Green; Neoplasms; Adenosine Triphosphate; Adenosine; Mice, Inbred C57BL; Apyrase; Female; Phototherapy
PubMed: 38915007
DOI: 10.1186/s12951-024-02643-w -
BMC Women's Health Jun 2024The purpose of this study was to predict the risk factors for residual lesions in patients with high-grade cervical intraepithelial neoplasia who underwent total...
BACKGROUND
The purpose of this study was to predict the risk factors for residual lesions in patients with high-grade cervical intraepithelial neoplasia who underwent total hysterectomy.
METHODS
This retrospective study included 212 patients with histologically confirmed high-grade cervical intraepithelial neoplasia (CIN2-3) who underwent hysterectomy within 6 months after loop electrosurgical excision procedure (LEEP). Clinical data (e.g., age, menopausal status, HPV type, and Liquid-based cytology test(LCT) type), as well as pathological data affiliated with endocervical curettage (ECC), colposcopy, LEEP and hysterectomy, were retrieved from medical records. A logistic regression model was applied to estimate the relationship between the variables and risk of residual lesions after hysterectomy.
RESULTS
Overall, 75 (35.4%) patients had residual lesions after hysterectomy. Univariate analyses revealed that positive margin (p = 0.003), glandular involvement (p = 0.017), positive ECC (p < 0.01), HPV16/18 infection (p = 0.032) and vaginal intraepithelial neoplasia (VaIN) I-III (p = 0.014) were factors related to the presence of residual lesions after hysterectomy. Conversely, postmenopausal status, age ≥ 50 years, ≤ 30 days from LEEP to hysterectomy, and LCT type were not risk factors for residual lesions. A positive margin (p = 0.025) and positive ECC (HSIL) (p < 0.001) were identified as independent risk factors for residual lesions in multivariate analysis.
CONCLUSIONS
Our study revealed that positive incisal margins and ECC (≥ CIN2) were risk factors for residual lesions, while glandular involvement and VaIN were protective factors. In later clinical work, colposcopic pathology revealed that glandular involvement was associated with a reduced risk of residual uterine lesions. 60% of the patients with residual uterine lesions were menopausal patients, and all patients with carcinoma in situ in this study were menopausal patients. Therefore, total hysterectomy may be a better choice for treating CIN in menopausal patients with positive margins and positive ECC.
Topics: Humans; Female; Uterine Cervical Dysplasia; Hysterectomy; Retrospective Studies; Middle Aged; Risk Factors; Adult; Uterine Cervical Neoplasms; Neoplasm, Residual; Papillomavirus Infections; Margins of Excision; Electrosurgery; Aged
PubMed: 38915002
DOI: 10.1186/s12905-024-03212-x -
Transplantation and Cellular Therapy Jun 2024Second allogeneic hematopoietic cell transplantation (HCT2) is potentially curative for adults with AML or myelodysplastic neoplasm (MDS)/AML experiencing relapse after...
BACKGROUND
Second allogeneic hematopoietic cell transplantation (HCT2) is potentially curative for adults with AML or myelodysplastic neoplasm (MDS)/AML experiencing relapse after a first allograft (HCT1), but prognostic factors for outcomes are poorly characterized.
OBJECTIVES
To provide a detailed analysis of HCT2 outcomes and associated prognostic factors in a large single-center cohort, with a focus on identifying predictors of relapse and non-relapse mortality (NRM).
STUDY DESIGN
We studied adults ≥18 years who underwent HCT2 at a single institution between April 2006 and June 2022 for relapsed AML (n=73) or MDS/AML (n=8).
RESULTS
With a median follow-up among survivors of 74.0 (range: 10.4-187.3) months, there were 30 relapses and 57 deaths, of which 29 were NRM events, contributing to the estimates for relapse, overall survival (OS), relapse-free survival (RFS), and NRM. Three-year estimates for relapse, RFS, and OS were 37% (95% confidence interval: 27-48%), 32% (23-44%), and 35% (26-47%). The rate of NRM at 100 days and 18 months was 20% (12-29%) and 28% (19-39%). Outcomes differed markedly across patient subsets and were substantially worse for patients who underwent HCT2 with active disease (i.e. morphologic evidence of bone marrow and/or extramedullary disease), for patients who relapsed ≤6 months after HCT1, and for patients with higher HCT-specific Comorbidity Index (HCT-CI) or Treatment-Related Mortality (TRM) score. After multivariable adjustment, active disease was associated with a higher risk of relapse (HR=3.19, p=0.006) and shorter RFS (HR=2.41, p=0.008) as well as OS (HR=2.17, p=0.027) compared to transplant in morphologic remission without multiparameter flow cytometric evidence of measurable residual disease (MRD). Similarly, a relapse-free interval <6 months after the first allograft was associated with higher risk of relapse (HR=5.86, p<0.001) and shorter RFS (HR=2.86; p=0.001) and OS (HR=2.45, p=0.003). Additionally, a high HCT-CI score was associated with increased NRM (HR=4.30, p=0.035), and shorter RFS (HR=3.87, p=0.003) and OS (HR=3.74, p=0.006). Likewise, higher TRM scores were associated with increased risk of relapse (HR=2.27; p=0.024) and NRM (HR=2.01, p=0.001), and inferior RFS (HR=1.90 p=0.001) and OS (HR=1.88, p=0.001).
CONCLUSIONS
A significant subset of patients with AML or MDS/AML relapse after HCT1 are alive and leukemia-free 3 years after undergoing HCT2. Our study identifies active leukemia at the time of HCT2 and early relapse after HCT1 as major adverse prognostic factors, highlighting patient subsets in particular need of novel therapeutic approaches, and supports the use of the HCT-CI and TRM scores for outcome prognostication.
PubMed: 38914227
DOI: 10.1016/j.jtct.2024.06.019 -
Neuro-oncology Jun 2024The 2016 and 2021 World Health Organization (WHO) 2021 Classification of Central Nervous System (CNS) tumors have resulted in a major improvement of the classification...
The biological significance of tumor grade, age, enhancement and extent of resection in IDH mutant gliomas: how should they inform treatment decision in the era of IDH inhibitors? Invited review.
The 2016 and 2021 World Health Organization (WHO) 2021 Classification of Central Nervous System (CNS) tumors have resulted in a major improvement of the classification of IDH-mutant gliomas. With more effective treatments many patients experience prolonged survival . However, treatment guidelines are often still based on information from historical series comprising both patients with IDHwt and IDH mutant tumors. They provide recommendations for radiotherapy and chemotherapy for so-called high-risk patients, usually based on residual tumor after surgery and age over 40. More up-to-date studies give a better insight into clinical, radiological and molecular factors associated with outcome of patients with IDH-mutant glioma. These insights should be used today for risk stratification and for treatment decisions. In many patients with an IDH-mutant grade 2 and grade 3 glioma, if carefully monitored postponing radiotherapy and chemotherapy is safe, and will not jeopardize overall outcome of patients. With the INDIGO trial showing patient benefit from the IDH inhibitor vorasidenib, there is a sizable population in which it seems reasonable to try this class of agents before recommending radio-chemotherapy with its delayed adverse event profile affecting quality of survival. Ongoing trials should help to further identify the patients that are benefiting from this treatment.
PubMed: 38912846
DOI: 10.1093/neuonc/noae107 -
Journal of Pediatric Hematology/oncology Jul 202418F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is a diagnostic tool widely used in adult oncology and some pediatric...
BACKGROUND/AIM
18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is a diagnostic tool widely used in adult oncology and some pediatric oncological settings. There are no established recommendations for the use of this imaging modality in pediatric malignant germ cell tumors (mGCT), however. Our aim is to evaluate the role of 18F-FDG PET/CT in the restaging of mGCT after chemotherapy in children and adolescents.
METHODS
We retrospectively reviewed patients with mGCT treated in Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers who underwent 18F-FDG PET/CT between 2011 and 2021.
RESULTS
Seventeen patients (median age 13 y) were included in the study. In 14 patients, 18F-FDG PET/CT was performed at diagnosis; 12 showed pathologic uptake. The 2 18F-FDG PET/CT negative cases were histologically defined as yolk sac tumor (YST) and mixed (chorioncarcinoma, YST). Nine of the 12 patients who had pathologic 18F-FDG PET/CT at diagnosis repeated the examination after neoadjuvant chemotherapy, before, second look surgery. In 5 cases, no pathologic uptake was evident. Histology showed necrosis alone in 4 cases and necrosis and mature teratoma in 1. In 3 of the 6 cases with pathologic uptake (2 of 6 patients did not perform the examination at diagnosis), histology showed persistence of malignant component, whereas in the remaining 3 cases, necrosis and mature teratoma were present.
CONCLUSION
In our review of a series of children with mGCT, 18F-FDG PET/CT after neoadjuvant chemotherapy showed 1 of 5 false negatives and was unable to discriminate between residual malignant component and mature teratoma.
Topics: Humans; Fluorodeoxyglucose F18; Adolescent; Child; Male; Neoplasms, Germ Cell and Embryonal; Retrospective Studies; Female; Positron Emission Tomography Computed Tomography; Child, Preschool; Radiopharmaceuticals
PubMed: 38912835
DOI: 10.1097/MPH.0000000000002882 -
Human Pathology Jun 2024Multiple myeloma (MM) is an incurable malignant plasma cell neoplasm, representing the second most common hematopoietic cancer. As plasma cell neoplasms are clonal and...
Multiple myeloma (MM) is an incurable malignant plasma cell neoplasm, representing the second most common hematopoietic cancer. As plasma cell neoplasms are clonal and often secrete a monoclonal protein (M-spike), laboratory diagnosis is usually straightforward, especially when ancillary studies such as immunohistochemistry, flow cytometry, and protein electrophoresis are available in addition to microscopic examination. Despite the repertoire of diagnostic tools, rare cases pose diagnostic dilemmas, especially when reagent antibodies do not react as expected, extent of disease is patchy, or when disease occurs in unique age groups. In this retrospective study, we report a series of challenging diagnostic cases, discussing aberrant findings and comparing them to more classic counterparts. Twelve cases collected during routine clinical sign-out were reanalyzed and include examples of MGUS, classic multiple myeloma, t(11;14) rearranged myeloma, minimal residual disease, AA and AL amyloidosis, truncated light chain, non-secretory and non-producer myeloma, biphenotypic myeloma, oligoclonal expansion after bone marrow transplant, and plasma cell leukemia in a young adult. This cohort showcases the diversity of atypical presentations of plasma cell neoplasms, and we highlight standardized approaches to workup to avoid diagnostic pitfalls.
PubMed: 38909710
DOI: 10.1016/j.humpath.2024.06.012 -
Journal of Controlled Release :... Jun 2024Peritoneal carcinomatosis (PC) is characterized by a high recurrence rate and mortality following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy...
Peritoneal carcinomatosis (PC) is characterized by a high recurrence rate and mortality following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC), primarily due to incomplete cancer elimination. To enhance the standard of care for PC, we developed two cationic liposomal formulations aimed at localizing a toll-like receptor agonist, resiquimod (R848), in the peritoneal cavity to activate the immune system locally to specifically eradicate residual tumor cells. These formulations effectively extended R848 retention in the peritoneum by >10-fold, resulting in up to a 2-fold increase in interferon α (IFN-α) induction in the peritoneal fluid, without increasing the plasma levels. In a CT26 colon cancer model with peritoneal metastases, these liposomal R848 formulations, when combined with oxaliplatin (OXA)-an agent used in HIPEC that induces immunogenic cell death-increased tumor infiltration of effector immune cells, including DCs, CD4, and CD8 T cells. This led to the complete elimination of PC in 60-70% of the mice, while the control mice reached humane endpoints by 30 days. The cured mice developed specific antitumor immunity, as re-challenging them with the same tumor cells did not result in tumor establishment. However, inoculation with a different tumor line led to tumor development. Additionally, exposing CT26 tumor antigens to the splenocytes isolated from the cured mice induced the expansion of CD4 and CD8 T cells and the release of IFN-γ, demonstrating long-term immune memory to the specific tumor. The anti-tumor efficacy of these liposomal R848 formulations was mediated via CD8 T cells with different levels of involvement of CD4 and B cells, and the combination with an anti-PD-1 antibody achieved a cure rate of 90%.
PubMed: 38909698
DOI: 10.1016/j.jconrel.2024.06.041