Current Oncology Reports最新文献

Purpose of review: Hypercalcemia of malignancy is one of the most common metabolic disorders in patients with cancer and is associated with significant morbidity and mortality. This narrative review summarizes pathophysiology, clinical presentation, diagnostic strategies, and therapies available for the management of hypercalcemia of malignancy in acutely ill adult patients.

Recent findings: We reviewed both classic and recent literature to provide practical recommendations for managing cancer-related hypercalcemia. Our findings are presented in the context of recently published societal guidelines. Timely identification and treatment of acute hypercalcemia of malignancy is vital. Understanding of the underlying disease processes and available therapies is needed to optimize patient care and healthcare resource utilization.

Retroperitoneal sarcomas (RPS) are a group of rare malignancies with many histologic types. Surgery is the hallmark of curative therapy for non-metastatic disease with the extent of resection depending on the histology. RECENT FINDINGS: Neoadjuvant therapies have limited response and efficacy in RPS; however, the benefit, regimen, and timing depend on histology. Innovative therapeutics are emerging and may prove promising. PURPOSE OF REVIEW: This review discusses the work-up, management, and advances in the field of retroperitoneal sarcoma.

Purpose of review: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine carcinoma that is primarily driven by Merkel cell polyomavirus (MCPyV) and ultraviolet radiation. Due to its rarity and innocuous appearance on clinical exam, MCC diagnosis is often delayed and therefore diagnosed at advanced stages. Overall survival outcomes are poor and notably worse than melanoma, with an estimated five-year survival ranging from 35 to 60% for stage I or II disease to < 15% for metastatic disease. Our review examines the diagnostic workup, prognostic markers, and current and emerging treatments of MCC.

Recent findings: For local disease in which surgical resection is feasible, tumor removal with potential adjuvant radiation therapy is the primary treatment modality. Immunotherapy with PD-1 / PD-L1 inhibitors is now standard for advanced disease where complete resection is not feasible. Additionally, there are many ongoing clinical trials examining novel immune checkpoint inhibitors, immunomodulators, targeted therapies, cellular therapies, vaccines, and oncolytic virus therapies with the goal of improving outcomes for patients with advanced disease or those who experience recurrence after first-line immunotherapy. MCC is an aggressive disease with a rapidly evolving treatment landscape, and emerging therapies hold the potential to improve prognosis in advanced disease.

Introduction: This study aimed to investigate the efficacy of imiquimod in Anal High Grade Squamous Intraepithelial Lesion (HSIL).

Methods: Electronic databases (Pubmed, MEDLINE, EMBASE and Cochrane Library databases) were searched from inception until December 2024 for articles reporting imiquimod as a treatment for anal HSIL.

Results: Five studies were identified (2 randomized controlled trials and 3 prospective non-randomized studies), containing data on 126 men of have sex with men living with HIV with anal HSIL. Most studies contained significant bias which prevented direct comparison. Reported complete response (CR) rates ranged between 14.3-78.6%, and 21.4-67% partial response (PR) rates of 3-weekly application for 16 weeks imiquimod course. A second course of imiquimod led to incremental response (CR 15-23.8%, PR 19-30%). Perianal HSIL showed superior response rates compared to intra-anal lesions (perianal HSIL CR ranging from 71.4 to 100%, intra-anal HSIL CR from 10.8 to 33.3%).

Discussion: In our systematic review we summarized the literature regarding imiquimod use for anal HSIL treatment, both perianal/intra-anal. Imiquimod can be proposed as a safe treatment of anal HSIL, and perianal HSIL may benefit more from imiquimod treatment. However, anal HSIL recurrence rates were high, and there are no long-term data on its efficacy. No studies investigated the role of imiquimod in women or in HIV- patients.

Conclusion: Imiquimod can be proposed as a safe option for treatment of anal HSIL.

Purpose of review: Since the introduction of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) as the first-line treatment for metastatic hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative (HR+/HER2-) breast cancer, there has been a significant expansion in the number of therapeutic options for subsequent lines of therapy. Many new agents are being studied, with potential for future regulatory approval. The increased number of therapeutic options raises questions about the optimal selection and sequencing of therapies for individual patients. These advances represent an important clinical challenge in this rapidly evolving field, given the introduction of new therapies targeting various pathways (alone or in combination) and new therapeutic classes being studied.

Recent findings: Recently approved targeted therapies have demonstrated improvements in progression free survival (PFS) for patients whose cancer harbors mutations in the PI3K/AKT pathway, ESR1, BRCA1/2, and/or PALB2. Data to support continuation of CDK4/6 inhibition after progression on a prior CDK4/6i remains mixed, though some studies suggest a subset of patients may benefit from this approach. Several agents with unique mechanisms of action have shown promise in data from early phase trials, and have the potential to enter the treatment lexicon in the coming years. Examples include CDK2- and CDK4-selective inhibitors, complete estrogen receptor antagonists (CERANs), proteolysis targeting chimeras (PROTACs), and next-generation PI3K pathway inhibitors. In this narrative review, we summarize the current and upcoming treatments for metastatic HR+/HER2- breast cancer after progression on a CDK4/6i plus ET, with a focus on the following: an overview of first-line regimens of CDK4/6i plus ET and observed mechanisms of resistance; currently approved second-line therapy options; and upcoming options currently under exploration in clinical trials. We focus primarily on new therapy classes that may offer therapeutic options beyond currently available treatments.

Purpose of the review: Assess new options and best sequence or combination strategies for the treatment of metastatic thymic epithelial tumors.

Recent findings: Besides historical cytotoxic chemotherapy regimens, which remain standard-of-care for many patients with thymoma, new options include antiangiogenic agents and immune checkpoint inhibitors (ICIs) in the first-line setting combined with carboplatin and paclitaxel for thymic carcinoma. Antiangiogenic agents are also used in the second-line setting, possibly sequenced or combined with ICIs. With the latter, comprehensive assessment for autoimmune disorders is advised, with subsequent close clinical and biological monitoring. Precision medicine strategies may be implemented with comprehensive genomic profiling and use of targeted agents. Multidisciplinary tumor board is key to optimize the treatment pathway for patients with metastatic thymic epithelial tumors, with a need for prospective studies assessing the best combination strategies.

Purpose of review: Diffuse tenosynovial giant cell tumor (D-TGCT) is a benign neoplasm with locally aggressive potential of the synovium, bursae, and tendon sheaths. This review summarizes the current treatment landscape for D-TGCT, with a focus on systemic therapies.

Recent findings: Surgery is the primary treatment option for tenosynovial giant cell tumor (TGCT), but there is a high risk of recurrence and associated morbidity, particularly for patients with advanced D-TGCT. Systemic therapies targeting the colony-stimulating factor 1 receptor (CSF1R) have resulted in positive tumor response, improved function, and decreased symptoms. For an alternative to surgery, the CSF1R inhibitors pexidartinib and vimseltinib are approved in the United States for TGCT, and other CSF1R inhibitors are in clinical development. CSF1R inhibitors represent a significant evolution in therapeutic strategies for D-TGCT. The potential risks and benefits of available treatments should be carefully considered in collaboration with a bone tumor-experienced, multidisciplinary team to determine the best course of care. Increased D-TGCT awareness and support through patient advocacy groups have helped to reshape the patient journey.

Purpose of review: Uveal melanoma (UM) is the most common intraocular malignancy in adults, representing a rare but aggressive melanoma subtype with a distinct molecular landscape, unique metastatic behavior and limited therapeutic options in the metastatic setting. This review provides an in-depth analysis of the latest evidence on the evolving treatment landscape of metastatic UM.

Recent findings: For liver-only metastatic disease, locoregional therapies provide significant benefit compared to systemic therapies. The recent approval of tebentafusp-tebn, a bispecific gp100 peptide-HLA-directed CD3 T-cell engager, marks a pivotal advancement for HLA-A*02:01-positive patients with unresectable/metastatic UM, demonstrating a clinically significant survival benefit. Several clinical studies are currently active, examining emerging locoregional and systemic treatments for metastatic UM, with promising early data. Despite effective local disease control through radiotherapy and enucleation, approximately 50% of patients develop metastatic disease, predominantly in the liver, with a median survival of less than one year. The approval of tebentafusp represents a landmark achievement in UM treatment, while promising experimental combinations have demonstrated clinical utility in late phase clinical trials, offering hope for further improvement in patient survival.

Purpose of review: Metabolic disorders significantly contribute to cancer burden globally. Uric acid (UA), a recognized metabolic risk factor linked to gout, also promotes insulin resistance, fatty liver, inflammation, and carcinogenesis. This systematic review evaluates UA's dual role in cancer, synthesizing epidemiological, mechanistic, and clinical evidence to clarify its potential as a therapeutic target.

Recent findings: The research of UA on cancer development mainly focuses on a clinical observational study, with limited molecular mechanism exploration. The associations between UA and cancer risk remain controversial, as sometimes the antioxidant, anti-inflammatory and immune-enhancing properties of UA are presented. There is lacking a systematic and updated review for summarizing the role of hyperuricemia on cancer risk and progression. The precise mechanism of UA in either enhancing or inhibiting cancer progression remains uncertain. Serum uric acid (SUA) exhibits paradoxical roles in cancer, with its effects varying by tumor type, concentration, gender, and disease stage. While UA predominantly drives tumorigenesis in most cancers, it shows protective effects in specific malignancies such as soft-tissue sarcoma and laryngeal squamous cell carcinoma, potentially through antioxidant activity at lower concentrations. Mechanistically, UA highly participate in the cancer risk and progression through reactive oxygen species (ROS) generation, disrupting T cell activation and dendritic cell maturation, exacerbating insulin resistance, and driving xanthine oxidoreductase (XOR) expression during the process of wound healing. Emerging clinical and mechanistic evidence highlights its oncogenic potential, underscoring the need for large-scale randomized controlled trials and cohort studies to clarify the relationship between hyperuricemia and cancer progression. Future research should prioritize exploring anti-UA therapies for cancer treatment, developing advanced animal models to dissect UA's mechanisms, and integrating diverse genomic datasets to unravel its context-dependent roles. Addressing these gaps will advance targeted strategies to leverage UA biology in cancer management.

Purpose of review: We conducted a scoping review to determine what is known about the prevalence and consequences of unmet social needs in U.S. cancer survivors, what screening tools are used to assess these needs, and what interventions have been developed to meet the needs of cancer survivors.  RECENT FINDINGS: We identified records from six databases. Inclusion criteria were peer-reviewed journal articles in English with empirical data from U.S.-based samples of people diagnosed with cancer as adults and assessing one of the following modifiable, individual-level needs commonly included in clinical screening: food insecurity, financial hardship, utility assistance, employment, housing, transportation, or personal safety. The search yielded 11,074 abstracts; 543 records underwent full-text review, and 189 were retained for data extraction. Most studies were quantitative and observational (88%), not based on theory (88%), and cross-sectional (87%). The majority addressed financial toxicity, commonly evaluated using the COmprehensive Score for financial Toxicity (COST). Fewer studies focused on food insecurity, transportation barriers, housing concerns, personal safety, or utility assistance. Included studies reported that financial toxicity and other social needs were negatively associated with health-related quality of life, mental health, and adherence to care.  Financial toxicity is now a well-established challenge for cancer patients, which suggests financial interventions may be widely beneficial. Future work is needed to develop a fuller picture of cancer survivors' other social needs, and to understand and address the impact of unmet social needs on clinical, health, and psychosocial outcomes.