Search Results (177)

Retinoblastoma is a success story in pediatric oncology, evolving from life-saving interventions to approaches that preserve eyes and vision while minimizing complications. Initially managed with enucleation and radiotherapy, treatment now emphasizes eye preservation through chemotherapy as the cornerstone therapy. Various chemotherapy delivery methods—including intravenous (IVC), intraarterial (IAC), intravitreal, intracameral, and periocular—offer flexibility in treatment. Studies show nearly 100% eye salvage rates for groups A–C. For advanced cases (groups D and E), IAC has achieved outcomes that were not possible before. Intravitreal injections, when performed safely, may help avoid enucleation and radiotherapy in advanced cases, preserving vision, even in complex scenarios, with vitreous seeding. Each strategy may be tailored to tumor and patient characteristics that may help optimize outcomes. Recent innovations like liquid biopsy, prenatal diagnosis, prognostic biomarkers, and new surgical methods, such as tylectomy and chemoplaque, are paving the way for more personalized care. While advanced extraocular or metastatic retinoblastoma remains challenging, these advancements underscore a shift towards better outcomes and individualized management. The future holds promise for refining treatment strategies to maximize eye and vision preservation while ensuring patient survival. Full article

Background: Invasive fungal infections (IFIs) are a major complication in patients with acute myeloid leukemia (AML), particularly during chemotherapy-induced neutropenia. Posaconazole is the standard drug for primary antifungal prophylaxis (PAP), but its use is limited by oral bioavailability and CYP3A4 interactions. Study Objective: This study aims to evaluate the clinical efficacy and safety of intravenous caspofungin versus oral posaconazole as PAP in AML patients during their first cycle of chemotherapy and assess their subsequent impact on clinical outcomes. Methods: A retrospective, monocentric study was conducted on 75 consecutive AML patients treated at the Federico II University Medical School of Naples, Italy (2021–2025). Patients received either caspofungin or posaconazole as PAP based on the drug–drug interaction risk or clinical conditions. IFIs were diagnosed using EORTC/MSG criteria. Logistic and Cox regression models were used to assess risk factors and overall survival (OS). Results: IFI incidence was 13.3% overall (9.4% proven/probable). No significant difference was found between the caspofungin and posaconazole groups (six vs. four IFIs; p = 0.878). Post-chemotherapy refractory AML (OR = 11.9; p = 0.003) and liver disease (OR = 30.4; p = 0.004) independently predicted IFI development. Median OS did not significantly differ in patients receiving caspofungin versus posaconazole (29.3 vs. 32.1 months, p = 0.6). Conclusions: Caspofungin appears clinically comparable to posaconazole for PAP in AML during the induction phase, especially when azole use is contraindicated. Prospective studies are warranted to refine prophylactic strategies in the era of new AML therapies. Full article

Background: Local recurrence for high-risk extremities/trunk soft tissue sarcoma (STS) after treatment can range from 15 to 30%. The modified Eilber protocol (MEP) using low-dose intravenous chemotherapy with a reduced dosage of radiation in the preoperative setting has demonstrated excellent local control and reduced wound complications in these patients. The aim of the current study was to assess long-term local control and overall survival in patients with STS treated with the MEP versus standard preoperative or postoperative radiotherapy. Methods: Patients diagnosed with STS from 2004 to 2016 were identified using the Alberta Cancer Registry. Patients with STS treated with the MEP, preoperative or postoperative radiotherapy, were included. Patient and tumor characteristics, treatments and outcomes were abstracted from the registry and primary chart review. Characteristics were compared using one-way ANOVA for continuous variable and chi-square test and Fisher test for the categorical outcomes. Local recurrence-free survival and overall survival were analyzed using Kaplan–Meier Analysis with Log-rank test. Results: A total of 242 patients with STS were included, among which 100 (41.3%) received the MEP prior to surgery, 91 (37.6%) had preoperative radiation, and 51 (21.1%) had postoperative radiation. After a median follow up of 4.9 years, there were no significant differences in local recurrence or local recurrence-free survival between patients treated with the MEP vs. preoperative or postoperative radiotherapy (10 vs. 6.6% and 7.8%, respectively, p-value NS). There were also no significant differences between groups for recurrence-free survival and overall survival. Conclusions: This study demonstrates that the use of the MEP has non-inferior oncologic outcomes compared to standard preoperative or postoperative radiation in a population-based analysis despite reducing the overall dosage of radiation administered. The modified Eilber preoperative chemoradiation protocol may be considered as an additional option for patients with STS. Full article

Background: Patient motion poses significant challenges for the accurate delivery of radiotherapy. In children undergoing proton beam therapy (PBT), up to 30 treatments under general anesthesia may be required over a period of 6 to 8 weeks. To date, the impact of this many iterative anesthetic exposures on patient outcomes remains unclear. Objective: The primary objective of this study was to assess the impact of iterative anesthesia with propofol-based total intravenous anesthesia (propofol-TIVA) on overall survival. The secondary objective was to assess the association between propofol-TIVA and the occurrence of an unplanned admission or emergency room visit within 30 days of treatment start. Methods: This was a retrospective study of children (≤19 years) who had undergone PBT (with or without anesthesia) for central nervous system disease. The Log-rank test and Cox proportional hazards models were used for analysis. Propensity score matching and E-value analyses were used to adjust for selection bias. Results: The average age of the 461 children included was 9.0 years (SD ± 4.9). The majority, 261/461 (56.6%), were male, and 267/461 (57.9%) had undergone PBT without anesthesia. The group who underwent PBT with propofol-TIVA were younger (4.7 years vs. 12.2 years, p < 0.001) and had higher proportions of patients with treatment interruptions (111/194 [57.2%] vs. 118/267 [44.2%], p = 0.006), chemotherapy history (64/194 [33.0%] vs. 18/267 [6.7%], p < 0.001), concurrent chemotherapy (37/194 [19.1%] vs. 27/267 [10.1%], p = 0.006), and unplanned admissions/emergency room visits (26/194 [13.4%] vs. 1/267 [0.4%], p < 0.001). Overall survival rates (propofol-TIVA vs. no anesthesia) at 1yr (94% vs. 96%), 2 years (88% vs. 90%), and 3 years (88% vs. 89%) were similar between patient groups (p = 0.558). In the multivariable analysis, PBT with propofol-TIVA was associated with increased odds of an unplanned admission/emergency room visit before (OR, 38.311; 95%CI, 5.139–285.580; p < 0.001) and after (OR, 42.012; 95% CI, 5.322–331.632; p < 0.001; E-value = 83.52) propensity score matching. Conclusions: In this retrospective study of children undergoing PBT for central nervous system disease, there was no association between anesthesia exposure with propofol-based total intravenous anesthesia and overall survival. However, PBT with propofol-based total intravenous anesthesia was associated with an increased risk of an unplanned admission/emergency room visit within 30 days of treatment start. Full article

Background: The anti-tumor response of the immune system is pivotal for treating triple-negative breast cancer (TNBC), particularly as targeted therapies are limited. However, the impact of immune-modulating factors such as the application of granulocyte-stimulating factors (G-CSFs) or infections, including febrile neutropenia, prophylactic or therapeutical application of oral antibiotics (OABs), and the need for intravenous antibiotics (IABs), on survival outcomes remains unclear. Methods: 1583 patients with early-stage TNBC enrolled in the SUCCESS A or C study underwent primary surgery, adjuvant chemotherapy, and radiotherapy if indicated. All patients had Eastern Cooperative Oncology Group (ECOG) status ≤ 2. The effects of G-CSF, OAB, and IAB application on overall survival (OS), invasive disease-free survival (iDFS), breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) were assessed. Results: Only IAB treatment was significantly associated with decreased survival in univariable analyses (OS: p = 0.003; iDFS: p = 0.036; BCSS: p = 0.011; DDFS: p = 0.044), while G-CSF and OAB administration were not. Adjusted multivariable Cox regressions including febrile neutropenia and dose reduction/shift, ECOG, age of patients, and other clinicopathological parameters confirmed a significant negative effect of IABs on OS (p = 0.020), BCSS (p = 0.018), and DDFS (p = 0.044). Conclusions: In summary, IABs during adjuvant chemotherapy seems to be a risk factor for inferior OS, BCSS, and DDFS in TNBC patients, possibly by affecting microbiome-related immune response modulation. Hence, preventive measures to avoid the need for IABs should be considered in these patients. Full article

Background/Objectives: This study aimed to explore the therapeutic potential of umbilical mesenchymal stem cell-derived apoptotic vesicles (UMSC-apoVs) in a 5-Fluorouracil (5-FU)-induced impairment in skin wound healing. Methods: UMSC-apoVs were isolated from UMSCs using differential centrifugation after the induction of apoptosis. A murine model was established by administering 5-FU via intravenous tail injection, followed by full-thickness skin wound creation. Mice received local injections of UMSC-apoVs at the lesion site. Wound healing was evaluated based on wound closure rates, histological analysis, and in vivo/in vitro functional assays. Rotenone (Rot)-pretreated UMSC-apoVs were used to explore the role of mitochondrial transfer between skin mesenchymal stem cells (SMSCs) and UMSC-apoVs in wound healing. Results: UMSC-apoVs significantly accelerated wound healing in 5-FU-treated mice, as demonstrated by enhanced wound closure rates and histological findings of reduced inflammatory infiltration and increased collagen deposition. UMSC-apoVs transferred mitochondria to SMSCs, enhancing viability, proliferation, and migration while reducing reactive oxygen species (ROS) production in SMSCs. Rot pretreatment inhibited the therapeutic effects of UMSC-apoVs on wound healing by inducing mitochondrial dysfunction in UMSC-apoVs. Conclusions: Our findings indicate that UMSC-apoVs improve 5-FU-induced impaired skin wound healing by facilitating mitochondrial transfer, suggesting a novel therapeutic strategy for alleviating chemotherapy-induced impairment in wound healing. Full article

Glioblastoma (GBM) is a difficult disease to treat for different reasons, with the blood–brain barrier (BBB) preventing therapeutic drugs from reaching the tumor being one major hurdle. The median overall survival is only 14.6 months after the standard first line of treatment. At relapse, there is no recognized standard second-line treatment. Our team uses intra-arterial (IA) chemotherapy as a means to bypass the BBB, hence achieving an overall median survival of 25 months. However, most patients eventually fail the treatment and progress. This is why we wish to expand our portfolio of options in terms of chemotherapy agents available for IA administration. In this study, we tested topotecan, cytarabine, and new formulations of carboplatin and paclitaxel by IA administration in the F98-Fischer glioma-bearing rat model as a screening tool for identifying potential candidate drugs. The topotecan IA group showed increased survival compared to the intravenous (IV) group (29.0 vs. 23.5), whereas the IV cytarabine group survived longer than the IA group (26.5 vs. 22.5). The new formulation of carboplatin showed a significant increase in survival compared to two previous studies with the conventional form (37.5 vs. 26.0 and 30.0). As for paclitaxel, it was too neurotoxic for IA administration. Topotecan and the new formulation of carboplatin demonstrated significant results, warranting their transition for consideration in clinical trials. Full article

The peritoneum is the second most common site of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Up to half of all patients that undergo curative-intent resection eventually develop peritoneal metastasis (PM), which accounts for significant morbidity and drives mortality. Despite recent advances in management, PM is associated with very poor prognosis, which is often measured in weeks to months. Clinical manifestations including bowel obstruction, ascites, and urinary obstruction have profound impact on quality of life. Even with relatively advanced disease, PM often remains occult on imaging and thus tend to be underdiagnosed and understudied. Many patients with peritoneal-only PM are excluded from clinical trials because response cannot be measured by standard radiographic criteria. Furthermore, as patients with PM are not eligible for surgical resection and low-volume peritoneal disease is often not amenable to percutaneous biopsy, tissue samples for peritoneal-specific translational studies are limited. Intraperitoneal therapeutics have been proposed as an attractive option for PM, as better penetration of tumor tissue can be achieved with less systemic toxicity compared with intravenous chemotherapy. Heated intraperitoneal chemotherapy (HIPEC), typically combined with cytoreductive surgery (CRS), is an option for select patients with PM from gynecologic or gastrointestinal primary, and for patients with primary peritoneal mesothelioma. However, the incorporation of locoregional therapy for PM in patients with PDAC has been poorly studied given the aggressive nature of pancreatic cancer and overall poor prognosis. With recent advances in existing treatment options, there may be a subset of patients who may derive benefits from locoregional control with cytoreduction and/or intraperitoneal chemotherapy. Critically, additional work is needed to determine PM-favorable clinical and tumoral predictive biomarkers to identify patients who may benefit from a more aggressive approach. We describe the current state of management of patients with peritoneal metastasis from PDAC and review the available data exploring peritoneal-directed therapy with cytoreductive surgery and/or intraperitoneal chemotherapy. Full article

Immune thrombocytopenia, formerly idiopathic thrombocytopenia purpura (ITP), is an autoimmune disease characterized by the depletion of platelets below 100,000/µL when other causes of thrombocytopenia have been ruled out. It is associated with several infectious pathologies, disease states, and as a known side effect and complication of several drugs and chemotherapies. Standard treatment calls for glucocorticoid-mediated immunosuppression, intravenous immunoglobin transfusion, platelet stimulation, platelet transfusion, and splenectomy in instances of chronic and severe disease. While standard treatments are often effective, some cases prove resistant, and more commonly, some patients are unable to tolerate standard treatment protocols or opt out of surgical intervention. In addition, second-line therapies can be unfeasibly expensive and are associated with side effects themselves. Therefore, for a subset of patients afflicted by immune thrombocytopenia, the exploration of alternative treatment methods is needed in order to ease their burden of disease. Emerging evidence suggests that plant-derived extracts, traditionally used in regions such as Asia and Africa to manage acute thrombocytopenia, hold promise as alternative or adjunctive therapies for the mentioned subset of patients. These natural compounds may provide a cost-effective and less invasive option, potentially bridging gaps in current treatment regimens. We propose these extracts may play a role in fulfilling this deficiency in current treatment protocols. With this review, we aim to characterize and compile evidence that various organic extracts and compounds may be utilized to improve outcomes in these patients. By highlighting their clinical relevance and potential for integration into ITP treatment protocols, this manuscript underscores the importance of expanding the alternative therapies for ITP to improve patient outcomes and reduce treatment burdens. Full article

The growing interest in minimal and non-invasive therapies, especially in the field of cancer treatment, highlights a significant shift toward safer and more effective options. Ablative therapies are well-established tools in cancer treatment, with known effects including locoregional control, while their role as modulators of the systemic immune response against cancer is emerging. The HIFU developed with magnetic resonance imaging (MRI) guidance enables treatment precision, improves real-time procedural control, and ensures accurate outcome assessment. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) induces deep coagulation necrosis within an elliptical focal area, effectively encompassing the entire tumor site and allowing for highly targeted radical ablation. The applications of MRgFUS in oncology are rapidly expanding, offering pain relief and curative treatment options for bone metastatic lesions. Additionally, the MRgFUS plays an effective role in targeted optional therapies for early prostate and breast cancers. Emerging research also focuses on the potential uses in treating abdominal cancers and harnessing capabilities to stimulate immune responses against tumors or to facilitate the delivery of anticancer drugs. This evolving landscape presents exciting opportunities for improving patient outcomes and advancing cancer treatment methodologies. In neuro-oncology, MRgFUS utilizes low-intensity focused ultrasound (LIFU) along with intravenous microbubbles to open the blood-brain barrier (BBB) and enhance the intra-tumoral delivery of chemotherapy drugs. Full article

Background: Surgery, chemotherapy, and radiation often have limited utility for advanced metastatic disease in the liver, and despite its promising activity in select cancers, PD-1 blockade therapy similarly has minimal benefit in this setting. Curaxin, CBL0137, is an experimental anti-cancer drug that disrupts the binding of DNA to histones, destabilizes chromatin, and induces Z-DNA formation which may stimulate anti-tumor immune responses. Methods: Murine cell lines of colon (CT26) and breast (4T1) cancer were interrogated for survival and CBL0137-associated DNA changes in vitro. Immunocompetent models of liver metastases followed by CBL0137 hepatic arterial infusion (HAI) were used to examine in vivo tumor cell DNA alterations, treatment responses, and the immune contexture associated with CBL0137, both alone and in combination with anti-PD-1 therapy. Results: CBL0137 induced immediate changes to favor tumor cell death in vitro and in vivo with an efficient tumor uptake via the HAI route. Toxicity to CBL0137 was minimal and anti-tumor treatment effects were more efficient with HAI compared to intravenous delivery. Immune effects were pronounced with CBL0137 HAI with concurrent depletion of a specific population of myeloid-derived suppressor cells and maintenance of effector T cell populations. Conclusions: Combination of CBL0137 HAI with PD-1 blockade improved survival in 4T1 tumors but not in CT26 tumors, and therapeutic efficacy relies on the finding of simultaneous and targeted depletion of myeloid-derived suppressor cells and skewing of T cell populations to produce synergy with PD-1 blockade therapy. Full article

Leuconostoc pseudomesenteroides is a rare pathogen that can cause bacteremia in immunocompromised patients, particularly those with hematological conditions like acute myeloid leukemia. In this case, a 56-year-old woman developed Leuconostoc bacteremia following chemotherapy and multiple infections, including invasive aspergillosis. Despite broad-spectrum antibiotic treatments, her fever persisted until the blood cultures identified Leuconostoc pseudomesenteroides. Switching to intravenous ampicillin led to the resolution of symptoms. This case highlights the challenges in diagnosing and treating rare, glycopeptide-resistant bacteria in immunosuppressed patients and underscores the importance of repeated blood cultures and automated diagnostic systems. It also highlights the need for more rapid ways of diagnosing and treating such rare infections. Full article

Introduction: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) consists of the administration of aerosolized chemotherapy into the abdominal cavity of patients suffering from peritoneal carcinomatosis. Our aim was to review the evidence supporting PIPAC in patients with peritoneal carcinomatosis from colorectal cancer. Methods: A systematic review was performed in accordance with the 2020 PRISMA guideline. MEDLINE and CENTRAL were searched using combinations of terms including “Peritoneal carcinomatosis”, “Peritoneal metastasis”, “PIPAC”, “Pressurized intraperitoneal aerosol chemotherapy” and “Colorectal cancer”. Original studies, in English, including patients treated with PIPAC for colorectal peritoneal carcinomatosis, were considered eligible. Case reports, non-English or French language articles and secondary analyses were excluded. Results: A total of 385 articles were screened and 374 articles were excluded, leaving 11 publications for inclusion in the qualitative analysis. The included studies totalized 949 patients who received PIPAC for peritoneal carcinomatosis due to colorectal cancer. The median peritoneal carcinomatosis index (PCI) ranged from 10 to 31. In all studies, the complete PIPAC protocol was achieved with an average of two to three 3 PIPAC sessions per patient. Oxaliplatin (OX) was used as a chemotherapeutic agent in all studies and could be associated with intravenous 5-FU and leucovorin. Most post-operative adverse events were recorded as mild to moderate with no intraoperative complications. Only four studies reported a decrease in the average PCI score for 50% of the patients. Median overall survival ranged from 8 to 37.8 months. Quality of life indicators were stable between PIPAC-OX cycles with a small but not statistically significant trend of improvement of most functional scales. Conclusions: PIPAC for peritoneal carcinomatosis from colorectal origin is feasible, safe and tolerable. Its impact on survival outcomes or quality of life remains to be demonstrated by randomized trials. Full article

Objectives: To compare the clinical outcomes of intravenous carboplatin/paclitaxel chemotherapy plus bevacizumab versus intraperitoneal cisplatin/paclitaxel chemotherapy without bevacizumab as the frontline treatment in women with advanced ovarian, fallopian tube and primary peritoneal cancer. Methods: Between November 2012 and January 2024, medical records of all consecutive women with stage II~IV cancer treated with either frontline adjuvant intraperitoneal cisplatin/paclitaxel without bevacizumab (IP group), intravenous carboplatin/paclitaxel without bevacizumab (IV group) or intravenous carboplatin/paclitaxel with bevacizumab (IVB group) at a tertiary referral center were reviewed. Results: A total of 143 women (IP group, n = 57; IVB group, n = 23; IV group, n = 63) were reviewed. The IP group had greater progression-free survival compared to the IVB group (49.1 months, 95% confidence interval [CI] = 27.8 months to infinity, versus 11.9 months, 95% CI = 11.2 to 16.2 months; adjusted hazard ratio [HR] = 0.45, 95% CI = 0.24 to 0.87, p = 0.017). Additionally, the IP group also had a higher overall survival compared to the IVB group (not reached, 95% CI = 55.6 months to infinity, versus 38.9 months, 95% CI = 21.9 months to infinity; adjusted HR = 0.34, 95% CI = 0.15 to 0.79, p = 0.012). Conclusions: Intraperitoneal cisplatin/paclitaxel chemotherapy without bevacizumab seems to offer a survival advantage when compared with intravenous carboplatin/paclitaxel with bevacizumab in the frontline treatment of women with advanced ovarian cancer. Full article

Objectives: This systematic review aimed to examine the efficacy and safety profile of amivantamab in patients with advanced or metastatic non-small cell lung cancer (NSCLC) and EGFR mutations. Methods: Three scientific databases, PubMed, Cochrane library and ClinicalTrials.gov were searched for relevant articles up until 30 June 2024. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and ≥3 grade adverse events (AE) were the outcomes of interest. Results: Five clinical trials were included in this systematic review, reporting data from 1124 patients (safety population; n = 1091 efficacy population), who received amivantamab as a monotherapy or in combination with other treatments, both in a first-line and in a relapsed/refractory setting. The median PFS for groups of patients that received amivantamab ranged from 4.3 to 8.3 months, while the lowest observed OS was 10.2 months. The ORR ranged from 30% to 73%. The rate of grade 3 or higher AEs ranged from 35% to 92%, while serious AEs ranged from 29% to 52%. Infusion-related reactions (IRRs) ranged from 42% to 78% among patients that received amivantamab intravenously, while a 13% IRR rate was found in a group of patients that received amivantamab subcutaneously. Conclusions: Current evidence suggests that amivantamab is an effective treatment option for patients with advanced or metastatic NSCLC with EGFR mutations. Amivantamab-based combinations may prolong survival both in the treatment of naïve patients and those who have progressed on chemotherapy or tyrosine kinase inhibitors. Full article