Chemotherapy最新文献

Introduction: Identifying the underlying mechanisms of immune checkpoint inhibitor resistance in patients with cachexia is a current challenge. Ghrelin is a peptide hormone that plays an important role in the metabolism of patients with cancer cachexia. Despite the importance of ghrelin in cancer cachexia, most previous studies on the subject have not distinguished between the forms of ghrelin.

Methods: We retrospectively screened patients with advanced or recurrent non-small cell lung cancer receiving PD-1/PD-L1 inhibitor monotherapy. Active and inactive ghrelin levels were measured in 100 patients with available plasma samples at immune checkpoint inhibitor initiation. Cancer cachexia was defined as weight loss of at least 5% during the past 6 months or weight loss of at least 2% with a BMI <20. We analyzed the associations of the active and inactive ghrelin levels and active-to-inactive ghrelin ratio (AIR) with cancer cachexia. The prognostic impact of the active and inactive ghrelin levels and AIR were also analyzed.

Results: Among 100 patients, 35 were diagnosed with cancer cachexia. The active ghrelin level and AIR were significantly associated with cancer cachexia, whereas the inactive ghrelin level was not. The active and inactive ghrelin levels and AIR were not associated with patient prognosis.

Conclusion: The active ghrelin level and AIR were associated with cancer cachexia but not with patient prognosis. The function of the active and inactive forms of ghrelin may differ in cancer patients. The form of ghrelin should be clearly mentioned in relevant studies on cancer cachexia.

Introduction: Doxorubicin (DOX), a potent anthracycline, is widely used in cancer therapy, but its effect is limited by doxorubicin-induced cardiotoxicity (DIC). Increasing evidence suggests that DIC is associated with ferroptosis, a cell death characterized by the iron-dependent accumulation of lipid peroxides. Although aerobic exercise is recommended for chemotherapy-related cardiac dysfunction, the extent to which its protective effects against DIC are mediated through the inhibition of ferroptosis remains largely unclear. The aim of this study was to elucidate the mechanism through which aerobic exercise attenuates DIC and provide theoretical support for promoting scientifically guided exercise in patients with DIC.

Methods: We conducted in vivo experiments involving 8 weeks of aerobic exercise during and after DOX treatment of C57BL/6J male mice, and in vitro experiments, H9c2 cells were treated with DOX and ferrostatin-1 (Fer-1, a ferroptosis inhibitor). Mice were randomly assigned into four groups: Control (C, n = 6), DOX (D, n = 10), aerobic exercise (E, n = 6) and DOX + aerobic exercise (DE, n = 10). Echocardiography was used to measure left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) to assess cardiac function in mice. ELISA kits were used to quantify serum biomarkers of myocardial injury, including cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), and lipid peroxidation markers, such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). Hematoxylin and eosin and Masson's trichrome were performed to evaluate myocardial structural damage. Fluorescent probes were used to detect ferrous iron (Fe2+), reactive oxygen species (ROS), and lipid peroxides in H9c2 cells. Western blotting was conducted to analyze ferroptosis-related proteins, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), acyl-CoA synthetase long-chain family member 4 (ACSL4), transferrin receptor 1 (TfR1), and ferritin heavy chain 1 (FTH1).

Results: DOX treatment significantly induced cardiac damage and dysfunction, as evidenced by disrupted myocardial tissue, increased myocardial fibrosis and cTnT levels, and decreased LVEF and LVFS. However, aerobic exercise effectively reduced cardiac structural and functional damage, and improved the rate of survival in mice. Furthermore, DOX-induced ferroptosis in cardiomyocytes both in vitro and in vivo, as marked by increased levels of Fe2+, ROS, and MDA, along with altered protein expression, including reduced FTH1 and SLC7A11 levels and increased ACSL4 levels. In contrast, aerobic exercise significantly mitigated these changes in vivo, and Fer-1 also effectively inhibited these effects in vitro.

Conclusion: Collectively, this study demonstrates that aerobic exercise alleviates DIC via the inhibition of ferroptosis.

Introduction: Evidence concerning the implementation of a therapeutic drug monitoring (TDM)-guided approach for optimizing isavuconazole exposure in onco-hematological pediatric patients is limited. The aim of this systematic review was to summarize the current evidence about the role that a TDM-guided strategy of isavuconazole may have in optimizing efficacy/safety outcomes of invasive fungal infection (IFI) treatment/prophylaxis among onco-hematological pediatric patients.

Methods: Two authors independently searched the PubMed-MEDLINE and Scopus databases up to 25 April 2025, to retrieve randomized controlled trials or observational studies providing real-life data assessing isavuconazole exposure according to a TDM-guided approach in pediatric patients, and evaluating the relationship between isavuconazole exposure and efficacy/safety outcomes. Data were independently extracted by the two authors, and the quality of the included studies was independently assessed by means of the Cochrane Risk of Bias Tool (RoB 2.0) in case of randomized controlled trials, and by means of the Newcastle-Ottawa scale in case of observational studies and case series. Mortality attributable to IFI and hepatotoxicity occurrence were selected as primary outcomes. Descriptive statistics were used for summarizing the retrieved data.

Results: After screening 577 articles, eight studies were included in the systematic review (five retrospective observational cohort studies and 3 case series; n = 116). Attainment of optimal isavuconazole exposure at first TDM assessment ranged from 36.7% to 83.3% of included patients, being underexposure reported in up to 40.0% of cases. Overall, mortality attributable to IFI occurred in 10 out of 59 patients (16.9%) in which this outcome was evaluated, being associated with isavuconazole underexposure only in 30.0% of cases. Hepatotoxicity occurred in 14 out of 78 included patients (17.9%), being related to isavuconazole overexposure in 50.0% of cases.

Conclusion: Despite limited findings, our systematic review may support a potential role for a TDM-guided strategy in optimizing isavuconazole exposure among onco-hematological pediatric patients, particularly considering both the non-negligible proportion of cases who failed in attaining optimal exposure with standard dosing regimens.

Introduction: Neoadjuvant chemotherapy (NAC) is extensively employed in breast cancer (BC), primarily for aggressive subtypes like triple-negative and human epidermal growth factor receptor 2 (HER2)-positive BC and in estrogen receptor-positive (ER+)/HER2- BC with high-risk features. In ER+/HER2- BC, pathological complete rates are much lower (<10%), while axillary dissection rates are higher. This study focuses on hormone receptor-positive (HR+)/HER2- BC patients undergoing NAC, examining its impact on pathological complete response (pCR) rates, with specific attention to tumor Ki67 and ER status.

Methods: Retrospective data analysis from Kartal Dr. Lütfi Kırdar City Hospital included HR+/HER2- BC patients who received NAC. Clinicopathological factors, NAC response, and surgical outcomes were assessed. Statistical analyses evaluated the association between Ki67, ER status, and pCR.

Results: Of 203 patients, 11.8% achieved pCR. Ki67 (p < 0.001) and ER percentage (p < 0.001) significantly correlated with pCR. Higher Ki67 was associated with increased pCR likelihood (HR: 1.03, 95% CI: 1.01-1.05). A Ki67-pCR probability curve revealed a cutoff of 23.5%. ER%-pCR analysis showed decreasing pCR rates with higher ER percentages. Multivariate analysis confirmed Ki67 (p = 0.003, HR: 1.02) and ER percentage (p = 0.019, HR: 0.97) as independent predictors of pCR probability.

Conclusion: Consideration of Ki67 and ER percentage aids in NAC decisions for HR+/HER2- BC, identifying patients with high NAC response rates, facilitating axillary preservation, and potentially avoiding axillary dissection. The pCR rates in patients with Ki67 ≤24 are particularly low, especially in patients with a high ER percentage. In these cases, upfront surgery and adjuvant treatment should be considered instead of NAC.

Background: Positron emission tomography (PET) with the use of 18F-fluorodeoxyglucose (FDG), implemented with low-dosage computer tomography, is to be considered as the most important evolution of imaging in the management and assessment of classical Hodgkin lymphoma patients.

Summary: According to Lugano response criteria, FDG-PET is mandatory to define metabolic response to frontline therapy and moreover it is important in the definition of nonresponders or refractory disease patients. Refractory disease is reported in about 15% of patients, with some variations based on the choice of first-line chemotherapy, and particularly in advanced stages, up to 40% eventually relapse within 3 years.

Key messages: The aim of this review was to highlight a practical way to use FDG-PET in the subset of HL, with some notes of its use in first-line patients, and particularly centered on relapsed or refractory setting with a final focus of the evaluation of response by FDG-PET in the new treatment era of immunocheckpoint inhibitors.

Introduction: There is little evidence regarding the safety and efficacy of the combination of abemaciclib plus radiotherapy (RT). The majority of studies investigated the combination of RT with palbociclib or ribociclib reporting that hematological toxicity is common. Given the unique toxicity profile of abemaciclib with greater gastrointestinal toxicity compared to hematological toxicity, we wanted to evaluate the toxicity of the combination with RT in metastatic breast cancer (BC) patients.

Methods: Patients with histologically proven metastatic or locally advanced BC treated with RT and concurrent abemaciclib were selected. Toxicity was assessed according to the NCI-CTCAE V4.0.

Results: Thirty-two metastatic sites were treated in 19 patients and analyzed. All patients received abemaciclib during the RT course. A total of 68% of patients received a full dose of abemaciclib during RT. Also, 71.9% of patients received a palliative intent (median dose = 30 Gy, range = 8-30 Gy), and 26.3% were treated for 9 oligo-metastatic or oligo-progressive sites of disease with stereotactic body RT (median dose = 30 Gy, range 21-30 Gy, given in 3-5 fractions). Overall, the rate of G3 toxicity was 15.7%. The rate of G3 hematological toxicity was 10.6% (2/19 patients, one G3 neutropenia and one G3 anemia). No patient presented diarrhea, including those treated for RT sites close to the bowel. One patient developed G3 skin toxicity. Pain significantly improved after RT (mean value NRS pre-RT = 3.9, SD = 3.07; mean value NRS after RT = 0.9, SD = 0.46; p < 0.0001).

Conclusion: Abemaciclib and concomitant RT seem well tolerated showing acceptable toxicity.

Introduction: Acute eosinophilic pneumonia (AEP) is a rare respiratory condition caused by eosinophil accumulation in the pulmonary tissue that can be related to drug administration. Daptomycin, an antibiotic active against gram-positive bacteria, is one of the leading causes of AEP among drugs. In order to raise awareness of this rare syndrome, in our work we have described a case of an 82-year-old male with Enterococcus faecalis endocarditis treated with daptomycin, who developed a daptomycin-induced AEP. We have performed a systematic review of the literature for all similar reported cases.

Methods: The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. To conduct the analysis, the terms "daptomycin AND eosinoph* AND pneum*" were entered into the databases Medline, CINAHL, and Embase on April 13, 2023. We considered all relevant records documenting AEP after daptomycin use. No restrictions in terms of year or language were made. A formal appraisal of observational studies was performed by Newcastle-Ottawa Scale. All results and data were reported by means of tables.

Results: Our search identified 93 relevant records, published between 2007 and 2023. A total of 120 patients were considered. Patients who experienced AEP were mostly males (n = 88, 73.3%) with a mean age of 68.28 years (SD 11.54). Daptomycin was most frequently prescribed for osteoarticular infections (n = 75, 62.5%) and to treat gram-positive cocci infections. The most frequently isolated pathogen was methicillin-resistant Staphylococcus aureus. Daptomycin was mostly used with off-label indications (n = 89, 74%). Symptoms of AEP were usually reported after a mean of 21.75 days of treatment (range 3-84) and typically included fever, dyspnea, dry cough, and acute respiratory failure. Reported treatment strategies invariably included daptomycin withdrawal, respiratory support, and corticosteroid treatment. One hundred and sixteen patients fully recovered. A fatal outcome was described in 4 patients. Suggestive symptoms and imaging raised suspicion for AEP, confirmed with bronchoalveolar lavage in 57.5% of the cases.

Discussion and conclusions: Daptomycin-induced AEP is a rare but potentially fatal complication, mostly reported after long treatment with daptomycin. Clinicians should be aware of this syndrome, as it could be initially misdiagnosed for an acute infectious respiratory syndrome, resulting in a delay in its diagnosis and treatment. Furthermore, since the risk of developing AEP is increased by longer drug exposure, caution should be used when discussing the use of daptomycin in longer treatment regimens.

Introduction: With the increasing use of blinatumomab in relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), including minimal residual disease (MRD)-positive cases, awareness of its adverse effects has gradually improved. Pneumocystis jirovecii pneumonia (PCP) associated with blinatumomab therapy is rare.

Case presentation: We present a case of PCP in a patient undergoing blinatumomab therapy. A 70-year-old female diagnosed with Philadelphia-like CRLF2 overexpression B-cell precursor ALL received blinatumomab as consolidation therapy after achieving complete remission with prior induction chemotherapy. On the second day of blinatumomab infusion, she developed intermittent low-grade fever, and chest computed tomography (CT) revealed subtle infiltrates and nodules. Despite empiric trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, she progressed to significant shortness of breath and type I respiratory failure, with increased lactate dehydrogenase and β-D-glucan assays. Chest CT showed diffuse ground-glass opacities with scattered small nodules. The dry cough prompted next-generation sequencing of peripheral blood, which tested positive for pneumocystis jirovecii without evidence of other pathogens. Consequently, the patient was diagnosed with PCP. The first cycle of blinatumomab had to be discontinued, and therapeutic dosages of TMP-SMX and dexamethasone were administered, resulting in full recovery and stable condition during follow-ups.

Conclusion: PCP is rare in B-cell precursor ALL patients receiving blinatumomab therapy but manifests with early onset and rapid disease progression. Despite prophylaxis, PCP infection cannot be ignored during blinatumomab therapy. Therefore, heightened attention is warranted when using blinatumomab therapy.

Introduction: Kodamaea ohmeri is an emerging fungus recognised as an important pathogen in immunocompromised hosts, responsible for life-threatening infections.

Case presentation: We describe a case of a 69-year-old immunocompetent man with a long history of leg skin ulcers infected by K. ohmeri. This is the first case of leg wounds infected by K. ohmeri in an immunocompetent patient. The infection was successfully treated with voriconazole 200 mg daily.

Conclusion: Though rare, K. ohmeri should be considered in patients with skin ulcers that are poorly responsive to medical treatment, even if not immunocompromised.