Current Treatment Options in Oncology最新文献

Opinion statement: The success of cancer care delivery must be evaluated not only by efficacy outcomes such as overall survival, but also by the experiences of patients and their informal caregivers throughout the course of care. Financial, time, and administrative burdens constitute a triad of non-physical "toxicities'' that greatly affect patient and caregiver experiences-and outcomes- and should be routinely considered and addressed in oncology practice. While all these burdens have been ever-prevalent, the increasing complexity of cancer care has made these issues more relevant over time. Financial and time burdens started receiving mainstream attention in the oncology community circa 2010 and 2020 respectively. Administrative burdens are currently less well defined but are increasingly recognized and consequential. Each component of the triad does not exist in isolation-financial, time, and administrative burdens can overlap with, interact with, and compound each other. Attempting to address one may worsen another-for example, transferring a medicine prescription and driving to another pharmacy 20 miles away where the co-pay is $50 lower may reduce direct medication out-of-pocket costs, but increase both time and administrative burden. The current piece summarizes the current status of the field with the hope it galvanizes the oncology community to understand and manage these burdens, so patients and caregivers can live their fullest lives.

Opinion statement: Melanoma is one of the most aggressive and lethal forms of skin cancer, with acral melanoma (AM) associated with the poorer prognosis among melanoma subtypes. Historically, it was considered that more extensive surgery could prolong survival; however, multiple randomized trials have demonstrated that greater surgical intervention does not improve survival. Over the past few years, novel therapeutic agents including immune checkpoint inhibitors and molecular-targeted drugs have remarkably improved prognosis of melanoma and potentially reduced the role of surgery. Furthermore, predictive models that integrate clinicopathologic features and gene expression profiling may further optimize patient selection and guidance for surgical de-escalation. In parallel, the use of these agents in adjuvant and neoadjuvant settings highlights the need for multimodal approaches combined with surgery. However, the landmark clinical trials have included few cases of AM, which is rare melanoma subtype in Western populations. Because of its unique molecular alterations, the applicability of findings from Western-based clinical trials to AM remains uncertain, leading to a lack of high-level evidence for this subtype. In this article, we review the available, albeit limited, evidence on surgical management for AM and discuss future perspectives and challenges for optimizing treatment strategies for this distinct melanoma subtype.

Opinion statement: As cardio-oncology matures, its continued inattention to the social determinants of health (SDOH) represents a critical blind spot in both clinical care and health equity. Despite growing recognition of how factors like income, housing, and transportation shape cardiovascular outcomes in cancer patients, their routine integration into care remains limited. This review underscores that implementation science frameworks such as RE-AIM, PRISM, and CFIR offer structured, evidence-informed pathways to translate knowledge into practice. With scalable strategies from EHR-based screening to community health worker interventions now available, the field is well-positioned to lead. Advancing equity in cardio-oncology requires not just awareness but deliberate, systematic action rooted in implementation science.

Opinion statement: Immunotherapy has revolutionized cancer treatment and dramatically improved outcomes across a broad range of malignancies. However, the expanding use of immune checkpoint inhibitors, monoclonal antibodies, Chimeric Antigen Receptor (CAR)-T cell therapies, bispecific T cell engagers, cytokines, and other immunotherapeutic approaches has brought forward a new spectrum of immune-related adverse events, among which cardiotoxicities-though relatively uncommon-are increasingly recognized as clinically significant and potentially life-threatening. These events range from fulminant myocarditis and arrhythmias to non-inflammatory left ventricular dysfunction, pericardial syndromes, and vascular inflammation, and often present diagnostic and management challenges due to their variable timing, severity, and underlying mechanisms. While immune checkpoint inhibitors remain the most studied in terms of cardiovascular toxicity, emerging evidence suggests that other modalities-including adoptive cell therapies and cytokine-based agents-also carry substantial cardiovascular risk, particularly through cytokine release syndrome, endothelial injury, or metabolic disruption. Understanding the pathophysiological mechanisms of these toxicities, including T-cell-mediated inflammation, mitochondrial dysfunction, and immune checkpoint dysregulation in the heart, is essential for early recognition and effective mitigation. As immunotherapies continue to expand in clinical use and combination regimens become more complex, there is a critical need for interdisciplinary cardio-oncology approaches that integrate cardiovascular risk assessment, monitoring, and tailored management strategies. Moving forward, identifying predictive biomarkers, optimizing surveillance protocols, and elucidating shared and therapy-specific mechanisms will be key to minimizing harm while preserving the oncologic efficacy of these transformative therapies.

Opinion statement: Peritoneal metastases (PM) in small bowel neuroendocrine tumors (SBNET) are challenging. These patients have worse oncologic outcomes and may have symptoms related to mechanical obstruction and hormone production. Difficult decisions apply in diagnosis, surgical selection, postoperative systemic therapy, and surveillance. To aid in these decisions, we routinely recommend obtaining somatostatin receptor based functional imaging (i.e. DOTA PET/CT) and arterial and venous phase CT preoperatively to evaluate disease burden and guide surgical planning. Disease biology should also guide surgical management. The presence of synchronous liver metastases should not exclude patients from surgery. For patients with PM and grade 1 or 2 well differentiated SBNETs, we recommend aggressive surgical cytoreduction with the goal of a completeness of cytoreduction (CC) of 0 or 1 and > 70% cytoreduction of liver metastases. For high grade (G3) well differentiated SBNETs, surgical intervention may still be considered. In patients where the extent of disease does not allow for effective cytoreduction, or where patient comorbidities preclude extensive surgery, palliative surgeries or interventions may be preferred. Postoperatively, radiologic surveillance is important to evaluate for disease progression. Some SBNET patients presenting without PM are at risk of developing PM in follow-up, especially those with liver metastases or high T stage. In patients with progression or inoperable disease, systemic therapy including somatostatin analogs (SSAs), chemotherapy or peptide receptor radionuclide therapy (PRRT) may be potential options, although the latter may pose increased risk of bowel obstruction. When cytoreducton and systemic therapy are no longer options, palliative measures should be employed. Because of this complexity, management of PM in SBNET patients is a multidisciplinary collaborative effort.

Opinion statement: Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma with an incidence of 0.008 to 0.045 cases per 100,000 per year, accounting for less than 1% of all soft tissue sarcomas. It mainly affects adults aged 30-50 years, usually on the trunk and proximal extremities. DFSP is Locally aggressive, with metastases occurring in up to 5% of cases, typically < 1%. Diagnosis is based on histology, including CD34 antigen expression and COL1A1-PDGFB fusion detection by FISH or RT-PCR. Mohs micrographic surgery is the mainstay of treatment, ensuring clear margins to minimise recurrence. Radiotherapy is used as adjuvant or preoperative therapy to improve Local control. Imatinib, a tyrosine kinase inhibitor, is highly effective in unresectable or metastatic DFSP, especially in cases with PDGFB mutations, achieving disease control in over 70% of patients and partial responses in 36%. The 10-year overall survival rate is 90.7%, although the fibrosarcomatous variant (DFSP-FS) has worse outcomes, with a 5-year Local progression-free survival rate of 33%. Rare metastases to the lungs, lymph nodes or brain are treated surgically; chemotherapy remains ineffective. We comprehensively reviewed the clinical data regarding DFSP, highlighting subtype differences (myxoid, pigmented, myoid, granular cell, sclerosing, atrophic, and fibrosarcomatous), as well as reconstruction methods.

Opinion statement: Malignant tumors of the distal tibia are rare and pose unique reconstructive challenges due to the region's complex anatomical and biomechanical characteristics. Contemporary treatment has progressively shifted from amputation to limb salvage. We believe that a favorable histologic response to neoadjuvant chemotherapy and the absence of major neurovascular involvement are key prerequisites for successful limb salvage. Amputation is generally considered a salvage option when limb salvage fails. In adults, we typically favor biological reconstruction combined with ankle arthrodesis as the first-line approach. For smaller defects, either allograft or distraction osteogenesis is recommended. For larger defects, we advocate for the use of recycled tumor-bearing autograft combined with fibular grafting. Non-biological reconstruction may be appropriate for patients who require immediate stability and early weight-bearing, but it is not recommended for patients with a life expectancy of several decades due to rising complication rates and progressive functional deterioration. For end-stage patients, the focus shifts to improving quality of life. We prefer simpler surgical procedures combined with nonsurgical oncologic care. In pediatric patients, preservation of the growth plate and joint is prioritized whenever oncologically safe. If preservation is not possible, a conventional non-expandable prosthesis is appropriate when the predicted limb-length discrepancy at skeletal maturity is less than 2 cm. Physeal distraction or an expandable prosthesis is preferred when the discrepancy is larger. Preoperatively, MRI and PET-CT are used for precise evaluation, along with multidisciplinary fracture risk prediction methods for fracture risk stratification. Intraoperatively, fluorescence guidance and computer assistance can enhance resection and reconstruction accuracy. However, several of these adjuncts remain under investigation. Ultimately, we individualize the surgical plan according to the patient's preferences while respecting local regulations and cultural or religious considerations.

Opinion statement: The management of muscle-invasive bladder cancer (MIBC) is evolving rapidly, with the integration of neoadjuvant and adjuvant therapies and biomarker-driven patient selection now essential to refining treatment decisions. While cisplatin-based neoadjuvant chemotherapy has been the standard of care, its underutilization due to toxicity and patient ineligibility underscores the need for alternative strategies. Immune checkpoint inhibitors and targeted therapies, particularly fibroblast growth factor receptor (FGFR) inhibitors and antibody-drug conjugates (ADCs) like enfortumab vedotin (Nectin-4-directed) and disitamab vedotin (human epidermal growth factor receptor 2 [HER2]-directed), have transformed the management of metastatic urothelial carcinoma and are now being investigated in MIBC. The next challenge is to deploy these agents rationally by using robust biomarkers. FGFR3 alterations are predictive of response to FGFR inhibitors, whereas HER2 over-expression is chiefly prognostic but may also predict benefit from HER2-targeted ADCs. Circulating tumor DNA (ctDNA) is both prognostic and predictive, guiding dynamic therapy escalation when positive and potential de-escalation when negative in ongoing perioperative trials. In the adjuvant setting, immune-checkpoint blockade has begun to change practice: nivolumab in CheckMate 274 and pembrolizumab in the Alliance AMBASSADOR study each produced a statistically significant improvement in disease-free survival for high-risk patients after radical cystectomy, with overall survival (OS) data still Maturing. More recently, the phase 3 NIAGARA trial showed that adding perioperative durvalumab to neoadjuvant gemcitabine/cisplatin, followed by surgery and adjuvant durvalumab, conferred significant gains in both event-free survival and OS compared with chemotherapy alone. ctDNA's role as a marker of minimal residual disease is especially compelling. Trials, such as IMvigor010, have laid the foundation for ctDNA's utility as an MRD Marker, while the IMvigor 011 and VOLGA trials are utilizing ctDNA-driven treatment escalation or de-escalation to enable appropriate patient selection. Moving forward, the integration of multi-omics technologies, liquid biopsies, and adaptive trial designs will be crucial in optimizing treatment strategies. Challenges remain in standardizing biomarker assays, validating their predictive value, and translating findings into routine clinical practice. Collaborative efforts and large-scale prospective studies are necessary to bridge existing gaps and advance precision medicine tailored for MIBC.

Opinion statement: The adrenocorticotropic hormone (ACTH)-secreting neuroendocrine neoplasms (NENs) represent a rare but frequently severe disease that is associated with poor prognosis, if not adequately managed. Treatment strategies vary according to the characteristics of the tumor and the severity of hypercortisolism. The optimal treatment is surgical resection of the NEN with a curative intent. In unresectable or metastatic tumors, medical control of hypercortisolism with concomitant treatment of NENs based on current guidelines is suggested. Steroidogenesis inhibitors are the principal choice to control hypercortisolism while bilateral adrenalectomy should be considered in cases of failure to control severe life-threatening hypercortisolism. Additionally, amongst the various anti-tumor systemic treatment options, peptide receptor radionuclide therapy (PRRT) seems to also be an effective option for the control of hypercortisolism. Preventive and curative treatment of cortisol-induced complications and comorbidities is also important to reduce morbidity and mortality. Overall, the management of ACTH secreting NENs may be very complex and requires an individualized approach in a multidisciplinary context to achieve the best and timely outcome for the patient.

Opinion statement: Plasminogen activator inhibitor-1 (PAI-1) plays a multifaceted and central role in the tumor biology of various skin malignancies. Beyond its classical function in fibrinolysis, PAI-1 contributes to tumor progression by promoting immunosuppression, angiogenesis, cellular senescence, and tissue remodeling. Its expression is particularly elevated in aggressive disease stages across cutaneous melanoma, cutaneous squamous cell carcinoma (cSCC), cutaneous angiosarcoma (CAS), and mycosis fungoides (MF), and is associated with poor clinical outcomes. The ability of PAI-1 to induce senescence-associated secretory phenotype (SASP), modulate PD-L1 expression, and recruit tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) suggests a key role in shaping the immunosuppressive tumor microenvironment (TME). This positions PAI-1 as both a potential biomarker for disease progression and a therapeutic target for restoring immune responsiveness, especially in tumors resistant to immune checkpoint inhibitors (ICIs). The PAI-1 inhibitor TM5614 has demonstrated promising activity in early clinical studies, particularly in anti-PD-1-refractory melanoma, and is currently under evaluation in multiple Phase II and III trials. Future strategies should focus on patient stratification using biomarkers such as SASP factors and PAI-1 levels, as well as rational combination therapies targeting interconnected pathways like IL-17/IL-23, AhR, and senescence signaling. Overall, PAI-1 inhibition offers a novel and mechanistically grounded approach to improve outcomes in skin cancers characterized by therapy resistance and an immunosuppressive microenvironment.