Cancer reports最新文献

Background

Intramedullary spinal cord metastasis (ISCM) is uncommon and usually occurs in advanced malignancies. Effective management methods are not clearly defined, and the outcomes of current treatments vary. Currently, there is no universal strategy for managing patients with intramedullary spinal metastases.

Case

To the best of our knowledge, we present a case of ovarian adenocarcinoma that was managed surgically in a 70-year-old woman with metastasis to the upper thoracic spinal cord, and we assess pertinent literature and deliberate management approaches.

Conclusions

Progression in early diagnosis and advanced therapeutic methods for ISCMs have contributed to the increased incidence and prevalence of this condition. There is no established consensus regarding the definitive patient management methods. Consequently, we offer multidisciplinary management with individualization based on the patient's functional status, requirement for a definitive diagnosis for potential additional adjuvant therapies, and assessment of the extent of systemic disease, which can influence the desired quality of life and survival duration.

Background

Tumor lysis syndrome (TLS) is a potentially life-threatening condition resulting from the rapid destruction of malignant cells, leading to electrolyte imbalances and severe complications, such as acute kidney injury, arrhythmias, and seizures. TLS can be managed through hyperhydration, urate-lowering treatments, and a steroid prophase strategy.

Aims

This study aims to explore the impact of fractionated rituximab, an anti-CD20 antibody, on the occurrence and severity of TLS during the initial cycle in patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL).

Methods

Data was retrospectively collected from 94 of 186 patients.

Results

Among the 94 patients included in the analysis, the median age was 70. Histologies were diffuse large B-cell lymphoma (75%), Burkitt lymphoma (13%) and high-grade B-cell lymphoma (8%). The majority were at an advanced stage (93%) with a high IPI score (75%). Most patients received anthracycline-containing regimens (72%) and prophylactic allopurinol (83%) and/or rasburicase (26%). Steroid prophase was administered to 82% of patients. The study identified one clinical TLS case and six laboratory TLS cases. Significant TLS factors included BL histology, elevated baseline LDH (⟩500 U/l), and rasburicase usage. Infusion reactions were rare (3%). Median progression-free survival was 2.6 years, and 2-year overall survival was 33%, irrespective of TLS occurrence.

Conclusion

In this real-life study, clinical TLS occurrence was low (1%). TLS appeared more frequent in BL but did not impact overall survival. Fractionated initial rituximab dosing in addition to preventive strategies is a feasible approach in preventing clinical TLS, warranting further prospective investigation.

Background

In this article, we review the most recent research on probiotics effects on diarrhea in both human and animal models of the condition along with the therapeutic potential of these compounds based on their findings.

Recent Findings

Nearly 50%–80% of cancer patients experience chemotherapy-induced diarrhea (CID), serious gastrointestinal toxicity of chemotherapeutic and radiation regimens that leads to prolonged hospitalizations, cardiovascular problems, electrolyte imbalances, disruptions in cancer treatment, poor cancer prognosis, and death. CID is typically categorized as osmotic diarrhea. The depletion of colonic crypts and villi by radiotherapy and chemotherapy agents interferes with the absorptive function of the intestine, thereby decreasing the absorption of chloride and releasing water into the intestinal lumen. Probiotic supplements have been found to be able to reverse the intestinal damage caused by chemo-radiation therapy by promoting the growth of crypt and villi and reducing inflammatory pathways. In addition, they support the modulation of immunological and angiogenesis responses in the gut as well as the metabolism of certain digestive enzymes by altering the gut microbiota.

Conclusion

Beyond the benefits of probiotics, additional clinical research is required to clarify the most effective strain combinations and dosages for preventing chemotherapy and radiotherapy diarrhea.

Background

Prostate cancer is the second leading cause of cancer deaths in men, second only to lung cancer. Despite this, diagnosis and prognosis methods remain limited, with effective treatments being few and far between. Traditionally, prostate cancer is initially tested for through a prostate serum antigen (PSA) test and a digital rectum examination (DRE), followed by confirmation through an invasive prostate biopsy. The DRE and biopsy are uncomfortable for the patient, so less invasive, accurate diagnostic tools are needed. Current diagnostic tools, along with genes that hold possible biomarker uses in diagnosis, prognosis and indications for personalised treatment plans, were reviewed in this article.

Recent Findings

Several genes from multiple families have been identified as possible biomarkers for disease, including those from the MYC and ETS families, as well as several tumour suppressor genes, Androgen Receptor signalling genes and DNA repair genes. There have also been advances in diagnostic tools, including MRI-targeted and liquid biopsies. Several personalised treatments have been developed over the years, including those that target metabolism-driven prostate cancer or those that target inflammation-driven cancer.

Conclusion

Several advances have been made in prostate cancer diagnosis and treatment, but the disease still grows year by year, leading to more and more deaths annually. This calls for even more research into this disease, allowing for better diagnosis and treatment methods and a better chance of patient survival.

Background

Thrombotic microangiopathy (TMA) is a pathological syndrome characterized by a combination of three key features: microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and organ damage, primarily affecting the kidneys. There are several drugs known to have a definite or probable causal association with TMA, and carfilzomib, a second-generation irreversible proteasome inhibitor (PI), approved for the treatment of multiple myeloma (MM), is one of them. In the medical literature, there have been a growing number of reports describing this serious adverse event occurring in MM patients. The precise mechanisms underlying the development of PI-induced TMA are not yet fully understood. Significant improvements in both renal and hematological aspects have been documented following the administration of eculizumab.

Recent Findings

In this report, we present two cases of MM patients who developed TMA while undergoing carfilzomib therapy. These cases were successfully treated at the Haematology Unit, Careggi Hospital in Florence. In our cases as well, the introduction of eculizumab resulted in rapid enhancements in renal function and platelet count, ultimately leading to the discontinuation of hemodialysis after 4 and 2 weeks, respectively.

Discussion and Conclusion

We assessed 91 patients who received carfilzomib-based therapies at our Haematology Department, during which we identified two cases of DITMA (2.2% incidence). Additionally, we conducted a literature review and discovered a total of 75 documented cases of carfilzomib-induced TMA. Our experience aligns with the cases reported in literature: this adverse event can manifest at any point during treatment, regardless of the specific drug combinations used alongside carfilzomib. The initial and most crucial step in its management involves discontinuing carfilzomib therapy; therefore, recognizing TMA in a timely manner is of utmost importance. Eculizumab could play a role in improving and expediting the resolution of this potentially fatal adverse event, but further studies are needed.

In a MM patient receiving carfilzomib, presenting with anemia, thrombocytopenia, and impaired renal function, a carfilzomib-induced TMA should be suspected in order to discontinue the causative agent.

Background

Patient susceptibility to cytokine release syndrome (CRS) resulting from immune-modulating chemotherapy has profound implications for clinical outcome. This is particularly true for patients receiving CAR T-cell therapy. First-line pharmacotherapy for CRS includes the administration of the IL-6 receptor-binding monoclonal antibody tocilizumab, or tocilizumab and corticosteroids. Other agents, such as siltuximab, anakinra, and dasatinab are also being explored for refractory cases of CRS. This review summarizes the potential role of omega-3 fatty acids, that is, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at ameliorating CRS in cancer patients receiving immune-modulating chemotherapy, and is compared with current treatment strategies to reduce the severity of the inflammatory response.

Recent Findings

Selective blockade of specific proinflammatory mediators (e.g., IL-6) is effective, but carries a significant risk of serious opportunistic infections. In contrast, omega-3 fatty acids affect multiple triggers underlying the inflammatory response (i.e., prostaglandins, leukotrienes, transcription factors, and specialized proresolving molecules), and its major limitation is avoidance of hypertriglyceridemia, which can be managed by reducing the rate of intravenous administration. This discussion proposes a novel approach by continuous infusion of omega-3 fatty acids to modulate the intensity of the severe systemic inflammatory response from CRS. The purpose of this review is to highlight the potential clinical benefits of a specialized omega-3 fatty acids dosage form to mitigate the severity of CRS as a hypothetical alternative to current treatment.

Conclusion

Optimizing the formulation, for example, enriched fish oil that meets drug concentration standards for EPA and DHA, a continuous infusion rate, reductions in long-chain saturated fatty acids concentrations, and addition of medium-chain triglycerides to improve EPA + DHA utilization and physical stability are key pharmaceutical factors. This may result in a safer and more effective option than targeted abrogation of cytokines and consequent risks of adverse drug reactions, but will require formal study in randomized control trials in humans.

Background

Small cell lung cancer (SCLC) harbours the most aggressive phenotype of all lung cancers to correlate with its bleak prognosis. The aggression of SCLC is partially attributable to its strong metastatic tendencies. The biological processes facilitating the metastasis in SCLC are still poorly understood and garnering a deeper understanding of these processes may enable the exploration of additional targets against this cancer hallmark in the treatment of SCLC.

Recent Findings

This narrative review will discuss the proposed molecular mechanisms by which the cancer hallmark of activating invasion and metastasis is featured in SCLC through important steps of the metastatic pathway, and address the various molecular targets that may be considered for therapeutic intervention. The tumour immune microenvironment plays an important role in facilitating immunotherapy resistance, whilst the poor infiltration of natural killer cells in particular fosters a pro-metastatic environment in SCLC. SCLC vasculogenesis is achieved through VEGF expression and vascular mimicry, and epithelial-mesenchymal transition is facilitated by the expression of the transcriptional repressors of E-cadherin, the suppression of the Notch signalling pathway and tumour heterogeneity. Nuclear factor I/B, selectin and B1 integrin hold important roles in SCLC migration, whilst various molecular markers are expressed by SCLC to assist organ-specific homing during metastasis. The review will also discuss a recent article observing miR-1 mRNA upregulation as a potential therapeutic option in targeting the metastatic activity of SCLC.

Conclusion

Treatment of SCLC remains a clinical challenge due to its recalcitrant and aggressive nature. Amongst the many hallmarks used by SCLC to enable its aggressive behaviour, that of its ability to invade surrounding tissue and metastasise is particularly notable and understanding the molecular mechanisms in SCLC metastasis can identify therapeutic targets to attenuate SCLC aggression and improve mortality.

Background

Recurrent squamous cell carcinoma (SCC) of the head and neck (SCCHN) remains a formidable clinical challenge despite available treatments. The phosphatidylinositol 3-kinase (PI3K) pathway has been identified as a potential therapeutic target, and alpelisib, a selective PI3Kα inhibitor, has demonstrated efficacy in certain malignancies. Combining this targeted therapy with immunotherapy has been suggested in previous studies as a promising strategy to bolster the immune response against cancer.

Cases

A 69-year-old woman with locoregional recurrence of PIK3CA-mutated SCC of the left maxilla and cervical nodal metastases. Several chemotherapeutic regimens, including cisplatin, docetaxel, 5FU, chemoradiotherapy, and mono-immunotherapy, resulted in disease progression. Alpelisib combined with pembrolizumab led to a sustained response for 9 months. A 58-year-old man with recurrent metastatic PIK3CA-mutated SCC of the oropharynx, involving the left lung, hilar, and mediastinal lymph nodes. Despite prior palliative radiation and platinum-based chemotherapy with pembrolizumab and cetuximab, treatment with alpelisib and nivolumab resulted in a partial response. Severe hyperglycemia and rash led to treatment discontinuation.

Conclusion

Our findings highlight the potential of this innovative therapeutic combination, suggesting a need for further investigations in this setting.

Objectives

Patients with multiple myeloma often require multiple treatment lines. The order in which treatments are sequenced has impact on clinical outcomes. This study aimed to estimate progression-free survival (PFS) and overall survival (OS) with common treatment sequences used in Portugal and the incremental benefit of an optimal sequence in transplant-ineligible patients with multiple myeloma.

Methods

A state-transition sequential model with a five-health state conceptual structure was developed to simulate and compare survival outcomes between treatment sequences up to four lines of treatments. Data sources included randomized clinical trials and indirect treatment comparisons. A panel of Portuguese hematologists listed four most common treatment sequences and optimal sequence of choice in transplant-ineligible patients.

Results

Our simulation estimated an OS between 6.1 and 7.8 years using the most common sequences, with VMP + DRd + Pd + Kd as the most effective (7.8 years). Optimal sequence of choice (DRd + PVd + Kd + Vd) achieved OS of 9.8 years and may extend OS in 2.0–3.7 years vs. most common sequences (26%–61% increase). This benefit was mostly explained by extended PFS in the first line of treatment.

Conclusion

Model results demonstrate that choosing the most effective treatment upfront is crucial in delaying disease progression thus yielding better survival outcomes in transplant-ineligible patients. There was a clear survival benefit in using daratumumab-based regimens in first line. This modelling exercise highlights the need to raise awareness around the impact of sequencing strategies to improve patient's outcomes.