Current Treatment Options in Oncology最新文献

Opinion statement: Over the past few years, treatment for advanced prostate cancer has begun shifting away from a one-size-fits-all approach toward biomarker-based therapies for select groups of patients. This review highlights the role of poly-ADP-ribose-polymerase (PARP) inhibitors in metastatic prostate cancer, emerging strategies to target the androgen receptor (AR), and innovative therapies aimed at cell surface proteins, including radioligand therapies, bispecific T cell engagers, and antibody-drug conjugates. For patients with homologous recombination repair (HRR)-mutated metastatic castration-resistant prostate cancer (CRPC), we favor combining a PARP inhibitor (PARPi) with an AR pathway inhibitor (ARPI), provided they can tolerate a more aggressive treatment strategy. In our opinion, patients with BRCA1 or BRCA2 mutations who are unable to handle combination therapy benefit from PARPi monotherapy. We are enthusiastic about the potential of ongoing clinical trials for new AR-directed therapies, such as AR ligand-directed degraders and CYP11A1 inhibitors, in metastatic CRPC. These treatments are expected to be most beneficial for patients whose cancer continues to rely on AR pathway signaling, suggesting they might also be effective in earlier stages of the disease. Progress in drug development and understanding of protein structures has led to new therapies that target cell surface proteins predominantly found in prostate cancer. We use ¹⁷⁷Lu-PSMA-617 for patients with PSMA avid metastatic CRPC who have progressed on an ARPI and a taxane chemotherapy. Additionally, we see promising potential in bispecific T-cell engagers (e.g., STEAP1-CD3 and PSMA-CD3) and novel radioligand therapies, including those utilizing actinium, to target these proteins. These advances show great promise in further enhancing survival for patients with metastatic prostate cancer.

Opinion statement: The therapeutic landscape for primary central nervous system lymphoma (PCNSL) continues to evolve, raising critical questions about the optimal integration of whole-brain radiotherapy (WBRT) to improve patient outcomes. Historically, WBRT has been a cornerstone in PCNSL management, offering effective disease control and relapse prevention. However, the use of high-dose WBRT (HD-WBRT) (≥ 36 Gy), while efficacious, has been associated with significant neurotoxicity, particularly in elderly patients, which has curtailed its long-term applicability. In recent years, high-dose chemotherapy combined with autologous stem cell transplantation (HDT-ASCT) has emerged as a consolidative treatment option, demonstrating efficacy comparable to WBRT, especially in younger patients and those with better performance status, thereby reshaping the therapeutic paradigm. As the therapeutic paradigm shifts, efforts to explore advances in WBRT techniques, such as dose reduction (23.4 Gy) and hyperfractionated protocols, have been aimed at mitigating neurotoxicity while maintaining therapeutic efficacy. These innovations make WBRT a viable option for carefully selected patient populations. Furthermore, this review explores emerging strategies, including localized radiotherapy, novel therapeutic combinations, and individualized treatment paradigms, while identifying key directions for future research to optimize outcomes for PCNSL patients.

Opinion statement: Mucosal melanoma is a rare and aggressive subtype of melanoma, accounting for 1%-2% of new cases in the United States in 2023, and 20%-30% in China and other Asian countries. Its origin is often occult, with the lack of early clinical features, the absence of actionable driver mutations, and poor response to immunotherapy, all contributing to its poor prognosis. The rarity of this subtype leads to limited awareness and interventions. Furthermore, due to its immune evasion mechanisms, mucosal melanoma shows resistance to traditional immune checkpoint inhibitors. Consequently, new therapeutic strategies are urgently needed to improve patient outcomes. Recent clinical trials have suggested that combination immunotherapy can overcome immune evasion, reduce resistance to treatment, produce synergistic anti-tumor effects, and improve survival. Epidemiological factors and clinical characteristics play significant roles in diagnosis and prognosis, while the mutational landscape influences responses to immunotherapy. This review provides an overview of these aspects and systematically discusses current research on combination therapies and emerging immunotherapy approaches for mucosal melanoma. It also explores potential future directions for treatment, aiming to enhance therapeutic strategies for this rare cancer and improve patient outcomes.

Opinion statement: The combination of stereotactic ablative radiotherapy (SABR) with immune checkpoint inhibitors, known as iSABR, marks a significant evolution in treating early-stage, inoperable non-small cell lung cancer (NSCLC). Managing these cases requires a multidisciplinary approach involving radiation and medical oncologists. Clinical evidence from a meta-analysis of seven studies, including 462 patients, indicates that iSABR may offer better outcomes than SABR alone. The analysis showed significantly improved progression-free survival (PFS) rates at 1-, 2-, and 3-year follow-ups for iSABR compared to SABR. There was also a trend toward better overall survival (OS) with iSABR. Subgroup analyses highlighted enhanced 3-year PFS with programmed death-1 (PD-1) inhibitors and doses per fraction ≥ 12.5 Gy. While iSABR slightly increased the risk of grade ≥ 3 adverse events like pneumonitis, fatigue, and skin reactions, these risks are generally manageable within a multidisciplinary treatment framework. In conclusion, iSABR demonstrates potential benefits and manageable risks in phase I/II trials for early-stage, inoperable NSCLC, with improved PFS and acceptable toxicity. These findings warrant further investigation in a larger phase III prospective randomized controlled trial to validate efficacy, optimize protocols, and establish long-term safety.

Opinion statement: The treatment of stage IVB cervical cancer is undergoing a paradigm shift, moving beyond palliation toward strategies that may improve survival rates in select patients. Radiation therapy is a key component of this shift, not only for local control, but also for enhancing systemic treatment efficacy and improving survival time. Stereotactic body radiation therapy (SBRT) for oligometastatic disease and image-guided brachytherapy improve tumor control while minimizing toxicity. The incorporation of immune checkpoint inhibitors into frontline therapy represents a significant advancement, particularly for PD-L1-positive tumors. However, durable responses remain a challenge, necessitating continued research into novel biomarkers and combination therapies. Personalized treatment approaches, integrating molecular profiling and adaptive therapy strategies, are essential for optimizing outcomes. Future clinical trials should evaluate the synergy between radiation and immunotherapy in order to refine curative approaches in stage IVB cervical cancer.

Opinion statement: Sexual health concerns are extremely prevalent among breast cancer survivors. The treatments used to treat and cure breast cancer - surgical removal of part or the whole breast, chemotherapy, radiation, and endocrine therapy - can have devastating impact on sexual function. Unfortunately, most patients are not given adequate preparation for these impending effects and can be blindsided by the resulting loss of sexual desire, vaginal dryness and decreased lubrication, pain with sex, vaginal stenosis, loss of nipple and breast sensation, muted or loss of orgasms and the resulting impact on sexuality and intimate relationships. Education about female sexual health is still lacking in most training programs and few cancer centers offer sexual health programs for cancer survivors. Oncology professionals and others who provide care for patients with breast cancer have the opportunity address sexual health, a vital aspect of quality of life. A focus on training and education, development of sexual health programs, and focus on sexual health in research is vital.

Opinion statement: Epithelioid hemangioendothelioma (EHE) is an ultra-rare sarcoma with a paucity of data on best practices for management. Pathogenic translocations involving the YAP or TAZ genes lead to constitutive activation of TEAD and TEAD-associated pathways. As our understanding of the molecular drivers of EHE has advanced, investigational treatment strategies have shifted away from cytotoxic chemotherapy toward more targeted approaches. This review focuses on the historical context and evolving landscape of systemic therapies for patients with EHE. For newly diagnosed patients, we recommend consultation at a high-volume sarcoma center whenever possible. If the disease is localized and resectable, surgical excision by a sarcoma-focused surgical oncologist is preferred. When the disease is unresectable, we first assess for disease progression to determine whether active surveillance is appropriate. Some patients may experience indolent, asymptomatic disease for years-or even decades-without requiring intervention. In patients with progressive or symptomatic unresectable disease, systemic therapy is warranted. Setting realistic expectations about the goals of treatment is essential, as no current systemic therapies reliably reduce tumor burden. However, molecular profiling and ongoing correlative studies from clinical trials may soon identify more effective therapeutic targets. For this reason, we encourage referral to centers that routinely perform molecular profiling and offer clinical trials with eligibility criteria for EHE, even to be considered as a first-line approach. Outside of a clinical trial, cytotoxic chemotherapy remains the frontline standard of care for patients who require systemic treatment. Importantly, treatment decisions must incorporate patient preferences and recognition that symptomatic improvement alone can be a meaningful outcome for preserving quality of life.

Opinion statement: Assessing cardiac risk prior to initiating breast cancer treatment, monitoring cardiac function during treatment, and implementing appropriate follow-up strategies are essential components of managing cardiotoxicity in breast cancer patients. A comprehensive cardiovascular evaluation should be conducted before treatment, including a detailed medical history, physical examination, and baseline cardiac imaging. Risk stratification tools can aid in determining the individual patient's risk profile. Close monitoring of cardiac function, including regular assessment of left ventricular ejection fraction (LVEF) and monitoring for signs and symptoms of cardiac dysfunction, is crucial during treatment. Prompt action should be taken if an adverse cardiovascular event is detected, including considering discontinuing or modifying the treatment regimen. Appropriate follow-up care is essential to monitor for long-term cardiac effects and optimize cardiovascular health in breast cancer survivors. Regular cardiovascular assessments, lifestyle modifications, and collaboration between healthcare professionals are important in managing cardiotoxicity effectively.

Opinion statement: Metastatic bone disease (MBD) is a significant source of morbidity and mortality in cancer patients with solid tumors, including those with gynecologic malignancies. Infiltration of tumor cells within the bone microenvironment disrupts bone homeostasis and leads to osteoblastic, osteolytic, or mixed bone lesions. Greater than two thirds of those with MBD experience cancer-induced bone pain (CIBP) and one to two-thirds will develop a skeletal-related event (SRE). Various pharmacologic, surgical, and radiation treatments exist for the palliation of bone metastases and the prevention of SREs. It is paramount to understand the diagnostic evaluation and evidence-based treatment paradigms of bone metastases to decrease healthcare utilization, alleviate financial burden, mitigate disability, and improve quality of life.

Opinion statement: The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) is rapidly evolving with the advent of PSMA-targeted radioligand therapies (RLTs) and bispecific T-cell engagers (BiTEs). These novel approaches provide new hope for patients who have progressed on standard therapies. However, their full clinical potential will be realized only by addressing key challenges, including tumor heterogeneity, resistance mechanisms, immune-related toxicities, and the immunosuppressive tumor microenvironment. Additionally, the optimal sequencing of these therapies at different stages of disease remains an open question. While most of these interventions are currently introduced in late-stage, heavily pretreated patients, ongoing clinical trials are exploring their role in earlier disease settings, where they may be more effective in altering the natural history of disease. PSMA-based RLTs, such as 177Lu-PSMA- 617, have demonstrated promising efficacy, particularly in patients with high PSMA expression. However, the presence of PSMA-negative or heterogeneous tumors necessitates the development of additional biomarkers and combination strategies. The ongoing PSMAddition trial may establish RLTs as an earlier-line treatment in hormone-sensitive metastatic prostate cancer, potentially shifting the standard of care. Moreover, mitigating toxicities through radioprotective agents may aid in expanding their clinical utility. BiTE therapies offer a different but complementary mechanism of action, leveraging T-cell engagement to drive tumor cell destruction. While cytokine release syndrome (CRS) and immunogenicity remain significant hurdles, modifications such as low-affinity CD3 binding and optimized dosing regimens are showing promise. The potential synergy of BiTEs with immune checkpoint inhibitors and tumor microenvironment-modulating agents should be further explored to enhance therapeutic efficacy. Given these advancements, the future of mCRPC treatment likely lies in a personalized, multimodal approach that integrates PSMA-based RLTs, BiTEs, and complementary therapies at earlier disease stages. Strategic biomarker-driven patient selection and combination regimens will be essential in optimizing outcomes while minimizing resistance and toxicity.