Search Results (83)

Background: Antineoplastic drugs are essential in the treatment of cancer; however, they are classified as hazardous due to their genotoxic, mutagenic, and carcinogenic properties. Healthcare professionals are at risk of exposure primarily through surface contamination. Despite international safety guidelines and technological innovations during the last decades, contamination remains a global occupational health challenge. Objective: This scoping review aims to identify and compare monitoring and detection methods, as well as cleaning and decontamination strategies, in relation to international occupational-safety standards. Methods: Following Arksey and O’Malley’s methodological framework and PRISMA-ScR reporting standards, the peer-reviewed literature and guidelines from 2000 to 2025 were reviewed. Studies were charted across three domains: contamination prevalence, monitoring/detection methods, and cleaning/decontamination effectiveness. Results: Evidence from twenty-two studies conducted in several countries worldwide demonstrated widespread surface contamination across hospital pharmacies, patient-care units, and outpatient facilities. Cyclophosphamide, ifosfamide, and methotrexate were the most frequently detected agents. LC—MS/MS wipe sampling remains the quantitative gold standard, while rapid immunoassay-based tools allow near real-time assessments but with reduced sensitivity. Cleaning protocols varied significantly: oxidizing and surfactant-based agents such as sodium hypochlorite and hydrogen peroxide achieved the highest removal rates (>90%) yet failed to eliminate residues completely. The included studies reported a wide range of monitoring, detection, and cleaning approaches used in healthcare settings. Conclusion: Surface contamination by antineoplastic drugs persists worldwide. Effective management requires harmonized contamination thresholds, validated cleaning strategies, adoption of rapid detection technologies, and continuous occupational surveillance. Full article

Background/Objectives: Penile squamous cell carcinoma (PSCC) is rare but aggressive. Systemic chemotherapy plays a crucial role in the management of node-positive or metastatic cases; however, the supporting evidence predominantly originates from small, non-randomized studies. This review provides a narrative analysis of the cytotoxic classes and regimens employed in PSCC and compares major clinical guidelines to facilitate informed decision-making in practice. Methods: English-language reports were identified in PubMed/Scopus/Google Scholar without date limits. Selection prioritized objective response, survival and toxicity outcomes, and guidance statements across neoadjuvant, adjuvant, and palliative settings. Results: Bleomycin-containing triplet regimens demonstrated efficacy but were associated with unacceptable pulmonary toxicity, leading to their discontinuation in clinical recommendations. Currently, cisplatin/taxane-based combinations remain fundamental in treatment protocols. The paclitaxel–ifosfamide–cisplatin (TIP) regimen achieves approximately 40–50% objective responses in phase II studies and may enable curative surgery, while taxane–cisplatin–5-fluorouracil (TPF) shows comparable efficacy with higher toxicity. For less fit patients, cisplatin–5-fluorouracil (PF) or carboplatin–taxane doublets are pragmatic alternatives. Single-agent taxanes or vinflunine offer modest second-line benefits. Although EAU–ASCO 2023, ESMO–EURACAN 2024, and NCCN v2.2025 are broadly in consensus, recommendations differ regarding eligibility thresholds and regimen preferences. Overall, the quality of the evidence remains low. Conclusions: TIP remains the reference neoadjuvant option for chemotherapy-fit patients with bulky nodal disease; doublets are reasonable when cisplatin fitness is limited; and bleomycin should be avoided. Harmonized eligibility criteria, biomarker-enriched studies, and coordinated multicenter trials are needed to improve outcomes in this rare malignancy. Full article

Purpose: Childhood cancers are the cause of treatment-associated morbidities, impairing functional mobility, participation and quality of life. Physical therapy is known to have a positive impact on health and well-being. Unfortunately, physical therapy is not utilized to its capacity. Thus, the aim of our study is to assess variables that facilitate utilization of physical therapy for children with oncological diagnoses across the continuum of care. Methods: A retrospective observational study of medical records was completed for children who received care at a large medical system. Descriptive statistics and multiple logistic regressions were performed. Results: Record review identified 16,975 episodes of care for 693 children. Of the 16,975, 240 included a referral to physical therapy. Of the 240, 178 used physical therapy. Presence of pain (odds ratio (OR) 20.026, p < 0.001), and being prescribed Ifosfamide or Daunorubicin (OR 28.213, p < 0.001; OR 15.439, p < 0.001, respectively) increased the likelihood of using physical therapy. Conclusions: We confirmed that physical therapy is underutilized for children with oncological diagnoses. However, clinical and socioeconomic variables were identified that facilitate use of physical therapy. Full article

Background: Ewing sarcoma (ES) is an aggressive malignancy and there is an unmet need for more effective treatment options for patients. Histone deacetylases (HDACs) have been shown to be involved in ES tumorigenesis and HDAC inhibitors have been investigated in the context of ES. Our objective for this study was to investigate the efficacy and mechanism of action of HDAC inhibition in vitro and in vivo in ES models, alone and in combination with standard of care therapies. Methods/Results: HDAC inhibitors were tested for in vitro efficacy against ES cell lines and romidepsin was found to be most effective. The mechanistic changes induced by romidepsin were investigated by Western blotting and proteins involved in cell cycle progression and DNA damage repair were found to be repressed. In vitro we identified that romidepsin synergizes with doxorubicin and etoposide and that it increases the efficacy of the standard of care combinations VDC/IE. Further, the combination treatments lead to an increase in caspase 3/7 cleavage, a decrease in DNA damage repair proteins, and an accumulation of DNA damage. In vivo, the combination of romidepsin and ifosfamide/etoposide (IE) leads to a significant decrease in tumor volume compared to that of IE alone. Conclusions: Our data indicates that romidepsin improves efficacy of chemotherapeutic agents in vitro and leads to a decreased tumor volume in vivo, suggesting that the addition of romidepsin may improve upfront treatment in ES patients. Full article

Cytostatics are contaminants of emerging concern. Their increasing presence in waste- and surface water is becoming a risk to aquatic life. Among them, 5-fluorouracil (5-FU) is one of the most frequently prescribed cytostatic drugs. 5-FU inhibits the thymidylate synthase activity, causing the depletion of thymidine nucleotides and misincorporation of uracil, and thus blocks DNA synthesis and replication. This study focuses on the influence of 5-FU on brackish and marine diatoms from the Baltic Sea, including Bacillaria cf. paxillifera, Gedaniella sp., Navicula perminuta, Nitzschia cf. aurariae, Skeletonema marinoi and Stephanocyclus meneghinianus, as well as natural microphytobenthos assemblages. The toxic effects of 5-FU were investigated in acute growth inhibition tests, which were performed using four types of media, i.e., artificial seawater with a salinity of 6.7, natural Baltic water, artificial seawater with a salinity of 22, and artificial seawater with the addition of cyclophosphamide and ifosfamide. The toxicity of 5-FU was checked for (1) each strain grown individually in all media, (2) six-strain mixed cultures grown in artificial seawater, and (3) natural microphytobenthic communities maintained in natural Baltic water. The diatom responses to 5-FU were species-specific. Growth conditions significantly modified the toxicity of 5-FU; tested strains were the most resistant to 5-FU when grown under optimal conditions, i.e., in natural Baltic water and/or at the optimal salinity. In the six-strain mixed cultures, higher 5-FU concentrations (>0.1 mg L⁻¹) shifted the dominance of diatom strains; the most resilient diatom S. meneghinianus replaced two other fast-growing strains, i.e., B. cf. paxillifera and Gedaniella sp. In the tested microphytobenthos assemblages, the highest biomass and species diversity were observed under the highest 5-FU concentrations (>5 mg L⁻¹). This indicated that the responses of complex species mixtures were governed by the ecophysiological features of their members and interactions among them, shaping the adaptive capacity of the entire assemblage. The introduction of the ecophysiological approach to toxicity testing seems to be crucial, and it would enable more realistic environmental risk assessment. Full article

Background/Objectives: Soft tissue sarcomas (STSs) are rare tumors arising from mesenchymal tissues, comprising over 100 distinct histological subtypes with varying biological behaviors, metastatic patterns, and treatment responses Despite advances in multimodal therapy, the overall survival of patients with metastatic STS is poor, mainly due to the weak response to conventional chemotherapy based on doxorubicin and ifosfamide. Methods: This review examines the evolution from traditional one-size-fits-all treatments to personalized medicine strategies, primarily focusing on assays based on patient-derived tumor samples, and it highlights their emerging role in guiding personalized treatment decisions and improving clinical outcomes in STS. These approaches, also known as functional precision oncology, are a step closer to the clinical situation as compared to other personalized therapies that rely on the identification of targetable genomic alterations using high-throughput technologies such as whole-genome sequencing, which have thus far failed to show convincing responses in STS treatment. Results: The main functional precision oncology platforms tested in patients with STS are in vitro cell viability tests, organoid cultures, and patient-derived xenografts. Each has advantages and limitations. In this context, in vitro drug sensitivity using cell suspension or organoids has shown a strong correlation with clinical responses. Furthermore, organoids matched the original tumor histology and microenvironment to a satisfactory degree. Establishment of xenografts proved feasible in the majority of patients; the technique could also preserve the tumor architecture and displayed high physiological relevance to the clinical situation. Conclusions: Although a major clinical study directly comparing conventional chemotherapy to personalized treatment guided by functional assays is yet to be published, this approach has gained popularity given the low efficacy of personalized medicine based on genetic alterations. The results thus far show promise for a better outcome for patients with metastatic STS. Full article

Study Aim: Patients with high-risk Ewing sarcoma (ES) have dismal outcomes despite aggressive multimodal therapy. This phase II, single-institution study evaluated the response rate to two up-front cycles of irinotecan, temozolomide, and temsirolimus (ITT) and assessed the tolerability of maintenance therapy following standard treatment in high-risk ES. Methods: Eligible patients had newly diagnosed high-risk ES (age ≥14 years old, metastatic disease, or primary pelvic tumor). The therapy included two cycles of window therapy (ITT) followed by interval-compressed chemotherapy (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide) and maintenance therapy (cyclophosphamide, sorafenib, and bevacizumab). A two-stage sequential design was employed to assess a >50% WHO response (CR or PR) with 80% power. Patients who required emergent radiation were excluded from receiving window therapy. Results: Sixteen patients (median age 12.2 years; range 4.8–23.6 years) were enrolled (12 evaluable for overall response, 10 for primary tumor response). Only three achieved a PR to window therapy, leading to study closure. All evaluable patients demonstrated a decline in their primary tumor volume (mean decline: 32.5%, standard deviation: 17.6%, p-value: 0.0005) and SUV peak (mean decline: 49.9%, standard deviation: 21.1%, p-value: 0.002). Maintenance therapy was well tolerated, with only 2/13 patients discontinuing due to toxicity. Conclusions: ITT did not achieve the prespecified response rate of 50%, according to WHO criteria; however, all patients exhibited decreased volume and metabolic activity, highlighting the limitations of conventional response assessments. Maintenance therapy was feasible and well tolerated. Although limited by small sample size, heterogeneous disease presentations, and the absence of a control arm, this study supports further evaluation of ITT and a maintenance approach in larger, randomized trials for high-risk ES. Full article

Malignant mediastinal tumors are a group representing some of the most demanding oncological challenges for early, multi-level, and successful management. The timely identification of any suspicious clinical symptomatology is urgent in achieving an accurate, staged histological diagnosis, in order to follow up with an equally detailed medical therapeutic plan (interventional or not) and determine the principal goals regarding efficient overall treatment in these patients. We report a case of a 24-year-old male patient with an incident-free prior medical history. An initial chest X-ray was performed after the patient reported short-term, consistent moderate chest pain symptomatology, early work fatigue, and shortness of breath. The following imaging procedures (chest CT, PET-CT) indicated the presence of an anterior mediastinal mass (meas. ~11 cm × 10 cm × 13 cm, SUV: 8.7), applying additional pressure upon both right heart chambers. The Alpha-Fetoprotein (aFP) blood levels had exceeded at least 50 times their normal range. Two consecutive diagnostic attempts with non-specific histological results, a negative-for-malignancy fine-needle aspiration biopsy (FNA-biopsy), and an additional tumor biopsy, performed via mini anterior (R) thoracotomy with “suspicious” cellular gatherings, were performed elsewhere. After admission to our department, an (R) Video-Assisted Thoracic Surgery (VATS) was performed, along with multiple tumor biopsies and moderate pleural effusion drainage. The tumor’s measurements had increased to DMax: 16 cm × 9 cm × 13 cm, with a severe degree of atelectasis of the Right Lower Lobe parenchyma (RLL) and a pressure-displacement effect upon the Superior Vena Cava (SVC) and the (R) heart sinus, based on data from the preoperative chest MRA. The histological report indicated elements of a combined, non-seminomatous germ-cell mediastinal tumor, posthuberal-type teratoma, and embryonal carcinoma. The imminent chemotherapeutic plan included a “BEP” (Bleomycin^®/Cisplatin^®/Etoposide^®) scheme, which needed to be modified to a “VIP” (Cisplatin^®/Etoposide^®/Ifosfamide^®) scheme, due to an acute pulmonary embolism incident. While the aFP blood levels declined, even reaching normal measurements, the tumor’s size continued to increase significantly (DMax: 28 cm × 25 cm × 13 cm), with severe localized pressure effects, rapid weight loss, and a progressively worsening clinical status. Thus, an emergency surgical intervention took place via median sternotomy, extended with a complementary “T-Shaped” mini anterior (R) thoracotomy. A large, approx. 4 Kg mediastinal tumor was extracted, with additional RML and RUL “en-bloc” segmentectomy and partial mediastinal pleura decortication. The following histological results, apart from verifying the already-known posthuberal-type teratoma, indicated additional scattered small lesions of combined high-grade rabdomyosarcoma, chondrosarcoma, and osteosarcoma, as well as numerous high-grade glioblastoma cellular gatherings. No visible findings of the previously discovered non-seminomatous germ-cell and embryonal carcinoma elements were found. The patient’s postoperative status progressively improved, allowing therapeutic management to continue with six “TIP” (Cisplatin^®/Paclitaxel^®/Ifosfamide^®) sessions, currently under his regular “follow-up” from the oncological team. This report underlines the importance of early, accurate histological identification, combined with any necessary surgical intervention, diagnostic or therapeutic, as well as the appliance of any subsequent multimodality management plan. The diversity of mediastinal tumors, especially for young patients, leaves no place for complacency. Such rare examples may manifest, with equivalent, unpredictable evolution, obliging clinical physicians to stay constantly alert and not take anything for granted. Full article

Background: Ifosfamide, an alkylating agent used for treating various cancers, can cause encephalopathy in 10–30% of adults and 8% of children. Methylene blue has been used to treat ifosfamide-induced encephalopathy (IIE). This study aimed to describe our institutional experience with IIE in children and young adults with cancer, including its clinical manifestations, treatment, and outcomes. Methods: We reviewed the clinical records of patients with cancer aged up to 30 years who developed IIE over 10 years. Results: Twenty-four patients (median age: 17.6 years, range: 4–30 years) were included; 54% were male, and 71% had bone/soft tissue sarcomas. Ifosfamide was administered alone or with other drugs (dose range: 1.5–3.3 g/m²/day). Twelve patients developed IIE after short intermittent infusions (1–3 h), and twelve developed it after continuous infusions (12–24 h). IIE occurred at a median cumulative ifosfamide dose of 18 g/m². Symptoms appeared within hours to five days and resolved within 24–120 h. An altered mental status was present in all except one patient. Twelve patients had grade 3 IIE (severe somnolence, agitation, and confusion), and five had grade 4 IIE (coma and seizures). Twenty patients (83%) received methylene blue, with symptom resolution in nineteen patients (83%). Imaging studies showed nonspecific findings. Ten patients were re-challenged with ifosfamide; five received prophylactic methylene blue treatment, of whom three had recurrence. Conclusions: IIE can occur with both short intermittent and continuous ifosfamide infusions and presents as an altered mental status, seizures, and, rarely, hemiparesis. Symptoms are transient, and methylene blue may help alleviate this neurotoxicity, but it does not completely prevent its recurrence. Full article

Background/Objectives: Locally advanced and metastatic leiomyosarcoma (LMS) is an aggressive cancer with limited treatment options. This single-institution, retrospective study evaluated the efficacy of first-line chemotherapy regimens in patients with advanced or metastatic LMS treated at Stanford Medical Center. Methods: Seventy-four patients with unresectable or metastatic LMS were deemed eligible and treated with first-line chemotherapy regimens, including gemcitabine plus docetaxel, dacarbazine, doxorubicin combinations (with evofosfamide or ifosfamide), and doxorubicin monotherapy. Progression-free survival (PFS), overall survival (OS), and disease control rate (DCR) were assessed using RECIST v1.1, with survival analyses performed using Kaplan–Meier and Cox proportional hazards methods. Results: The cohort consisted of 56 females (75.7%) and 18 males (24.3%), with a median age of 55.5 years. The majority (93.2%) had metastatic disease. The median PFS for the entire cohort was 4.9 months (range: 0.6–28.1 mo), and the median OS was 27.3 months (range: 1.9–140.2 mo). The doxorubicin combination (DC) group had the highest median PFS of 7.9 months (range: 0.6–15.8 mo). Doxorubicin alone had the highest median OS of 33.8 months (4.2–100.2 mo). Doxorubicin combinations demonstrated superior PFS in both uterine and non-uterine LMS subgroups. Conclusions: These findings reaffirm the efficacy of doxorubicin-based combination regimens as a first-line treatment for locally advanced and metastatic LMS, particularly in non-uterine LMS. Full article

Background/Objectives: Prior studies suggest that blood transfusion may adversely affect the survival of patients with cancer via transfusion-related immunomodulation. The objective of our study is to investigate the association between transfusion during neoadjuvant chemotherapy and survival in children, adolescent, and young adult (CAYA, 39 years old or younger) patients with osteosarcoma. Methods: This is a multicenter retrospective cohort study of patients between 2007 and 2022. Our primary exposure was receipt of any blood product in the neoadjuvant period (i.e., neoadjuvant transfusion). The primary outcome of interest was 3-year event-free survival (EFS) calculated using the Kaplan–Meier method, while secondary outcomes of interest included 5-year EFS and 3- and 5-year overall survival (OS). Firth multivariable logistic regression models were constructed to evaluate the adjusted association between transfusion status and 3- and 5-year EFS and OS. Results: In total, 73 patients were included in the analytic sample; among them, 34 received neoadjuvant transfusion. There was no significant difference between transfused and non-transfused groups in race, ethnicity, tumor location, stage at diagnosis, histologic response to neoadjuvant chemotherapy, and receipt of ifosfamide or radiation during initial treatment. The transfusion group included more females (p = 0.02) and lower median hemoglobin at diagnosis (p = 0.002) than the non-transfusion group. EFS and OS did not significantly vary by transfusion status or type. Conclusions: We did not observe an adjusted association between neoadjuvant transfusion and survival in CAYA patients with osteosarcoma. Full article

Background: Undifferentiated pleomorphic sarcoma (UPS) is a highly malignant mesenchymal tumor that ranks as one of the most common types of soft tissue sarcoma. Even though chemotherapy increases the 5-year survival rate in UPS, high tumor heterogeneity frequently leads to chemotherapy resistance and consequently to recurrences. In this study, we characterized the cell composition and the transcriptional profile of UPS with resistance to chemotherapy at the single cell resolution. Methods: A 58-year-old woman was diagnosed with a 13.6 × 9.3 × 6.0 cm multi-nodular tumor with heterogeneous cysto-solid structure at the level of the distal metadiaphysis of the left thigh during magnetic resonance tomography. Morphological and immunohistochemical analysis led to the diagnosis of high-grade (G3) UPS. Neoadjuvant chemotherapy, surgery (negative resection margins), and adjuvant chemotherapy were conducted, but tumor recurrence developed. The UPS sample was used to perform single-cell RNA sequencing by chromium-fixed RNA profiling. Results: Four subpopulations of tumor cells and seven subpopulations of tumor microenvironment (TME) have been identified in UPS. The expression of chemoresistance genes has been detected, including KLF4 (doxorubicin and ifosfamide), ULK1, LUM, GPNMB, and CAVIN1 (doxorubicin), and AHNAK2 (gemcitabine) in tumor cells and ETS1 (gemcitabine) in TME. Conclusions: This study provides the first description of the single-cell transcriptome of UPS with resistance to two lines of chemotherapy, showcasing the gene expression in subpopulations of tumor cells and TME, which may be potential markers for personalized cancer therapy. Full article

Methemoglobinemia is a potentially life-threatening, rare condition in which the oxygen-carrying capacity of hemoglobin is diminished. We present the case of a 3-year-old boy treated for T-cell acute lymphoblastic leukemia (T-ALL) who developed methemoglobinemia (MetHb 57.1%) as a side effect of ifosfamide administration. Due to his critical condition, the patient was transferred to the intensive care unit (ICU). The therapy included methylene blue administration, an exchange transfusion, catecholamine infusion, and steroids. Improving the general condition allowed for continuing chemotherapy without ifosfamide and completion of the HR2 block. Vigilance for methemoglobinemia as a very rare side effect should be widespread when using ifosfamide in the treatment protocols. Full article

Rhabdomyosarcoma (RMS) is a rare soft tissue sarcoma (STS) that predominantly affects children and teenagers. It is the most common STS in children (40%) and accounts for 5–8% of total childhood malignancies. Apart from surgery and radiotherapy in eligible patients, standard chemotherapy is the only therapeutic option clinically available for RMS patients. While survival rates for this childhood cancer have considerably improved over the last few decades for low-risk and intermediate-risk cases, the mortality rate remains exceptionally high in high-risk RMS patients with recurrent and/or metastatic disease. The intensification of chemotherapeutic protocols in advanced-stage RMS has historically induced aggravated toxicity with only very modest therapeutic gain. In this review, we critically analyse what has been achieved so far in RMS therapy and provide insight into how a diverse group of drug-metabolising enzymes (DMEs) possess the capacity to modify the clinical efficacy of chemotherapy. We provide suggestions for new therapeutic strategies that exploit the presence of DMEs for prodrug activation, targeted chemotherapy that does not rely on DMEs, and RMS-molecular-subtype-targeted therapies that have the potential to enter clinical evaluation. Full article

Background: The use of encapsulated cells for the in vivo delivery of biotherapeutics is a promising new technology to potentiate the effectiveness of cell-based therapies for veterinary and human application. One use of the technology is to locally activate chemotherapeutics to their short-lived highly active forms. We have previously shown that a stable clone of HEK293 cells overexpressing a cytochrome P450 enzyme that has been encapsulated in immunoprotective cellulose sulphate beads can be implanted near solid tumours in order to activate oxazaphosphorines such as ifosfamide and cyclophosphamide to the tumour-killing metabolite phosphoramide mustard. The efficacy of this approach has been shown in animal models as well as in human and canine clinical trials. In these previous studies, the oxazaphosphorine was only given twice. An analysis of the Kaplan–Meier plots of the results of the clinical trials suggest that repeated dosing might result in a significant clinical benefit. Aims: In this study, we aimed to (i) demonstrate the stable long-term expression of cytochrome P450 from a characterized, transfected cell clone, as well as (ii) demonstrate that one implanted dose of these encapsulated cytochrome P450-expressing cells is capable of activating multiple doses of ifosfamide in animal models. Methodology: We initially used cell and molecular methods to show cell line stability over multiple passages, as well as chemical and biological function in vitro. This was followed by a demonstration that encapsulated HEK293 cells are capable of activating multiple doses of ifosfamide in a mouse model of pancreatic cancer without being killed by the chemotherapeutic. Conclusion: A single injection of encapsulated HEK293 cells followed by multiple rounds of ifosfamide administration results in repeated anti-tumour activity and halts tumour growth but, in the absence of a functioning immune system, does not cause tumour regression. Full article