Current Treatment Options in Oncology最新文献

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: 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.

Opinion statement: Hematological malignancies are common among older adults, a group that faces unique challenges in treatment. While hematopoietic stem cell transplantation and CAR-T therapy offer promising, potentially curative and durable treatment options for older adults with high-risk diseases, their effectiveness can be limited by the individual's overall health and ability to tolerate intensive treatments. Conventional fitness assessments in this population often fall short in addressing the complexities of aging. Conversely, geriatric assessment provides a more comprehensive evaluation of an older adult's health across multiple domains, including physical health, cognitive function, mental health, nutrition, comorbidities, polypharmacy, and social support. This holistic approach helps to better understand the patient's resilience and facilitate timely adjustments to interventions, potentially improving both survival outcomes and quality of life. This review aims to explore the current evidence on integrating geriatric assessments into the optimization of older patients for hematopoietic stem cell transplantation and CAR-T therapy, along with various care models, their potential, and future directions.

Opinion statement: Pleural mesothelioma is an incurable cancer with unmet diagnostic and therapeutic needs. Due to its pattern of local spread, few patients are candidates for multimodality treatment and thus most patients only receive systemic therapy. Chemotherapy (pemetrexed plus platinum) was standard of care until the recent addition of immunotherapy (nivolumab plus ipilimumab, or pembrolizumab plus chemotherapy) as further first-line option. Physicians treating pleural mesothelioma should be aware of another option with Tumor Treating Fields (TTFields) therapy, a locoregionally-applied therapy utilizing electric fields generated by a portable medical device, and delivered to the tumor by skin-placed arrays. TTFields therapy delivered to the thorax using the NovoTTF- 100L device concomitant with pemetrexed and platinum agent is approved for unresectable pleural mesothelioma in the US, and received Conformité Européenne certification in Europe, based on results from the phase 2 STELLAR study (EF- 23; NCT02397928), where TTFields-related toxicity was limited to mild-to-moderate reversible skin reactions. Overall survival in the STELLAR study with TTFields therapy was 18.2 months, with further post-hoc analysis showing extended survival in patients with epithelioid histology. Within the evolving landscape of systemic treatments, TTFields therapy represents a novel and clinically versatile therapeutic option in the battle against pleural mesothelioma without introducing additional toxicities other than mild-to-moderate skin irritation. While promising, additional research is needed to optimize clinical application of TTFields therapy in patients with pleural mesothelioma, such as identifying the molecular determinants of therapy efficacy, and further investigation into the safe and effective delivery of TTFields therapy together with systemic agents, including immunotherapies.

Opinion statement: Penile cancer is a rare but aggressive malignancy, characterized by early lymphatic spread which is the most critical prognostic factor. Treatment options for patients with locally advanced and metastatic disease are limited, primarily relying on cisplatin-based chemotherapy, which is characterized by high toxicity and early resistance. In recent years, there has been a growing interest on translational research exploring the tumor microenvironment, enabling the identification of novel potential therapeutic targets. Emerging preclinical evidence supports the use of immune checkpoint inhibitors, antibody-drug conjugates and novel exploratory therapies targeting myeloid-derived suppressor cells and tumor associated macrophages, as well as their combinations. However, robust phase III trials investigating such therapies are currently lacking. A deeper understanding of the penile cancer immune landscape and the role of specific mutations in carcinogenesis, might lead to the development of novel combination strategies to overcome cisplatin resistance and disease progression, and to a better selection of patients for inclusion in future clinical trials.

Opinion statement: Serous endometrial intraepithelial carcinoma (SEIC) is an aggressive precursor and a similar biology to uterine serous carcinoma (USC). Patients diagnosed with SEIC should undergo surgical staging that includes total hysterectomy with bilateral salpingo-oophorectomy, lymph node sampling, and omentectomy. With trends in lymph node evaluation shifting towards sentinel lymph node sampling, we recommend bilateral sentinel lymph node sampling as a reasonable alternative to full pelvic and para-aortic lymphadenectomy. There is limited data to support the use of adjuvant chemotherapy, however, it is apparent that those with extrauterine disease have a higher likelihood of recurrence and decreased overall survival. Those with stage IVB SEIC have similar rates of survival to those with stage IVB USC and may be a population that could benefit from newer regimens for advanced stage endometrial cancer including immunotherapy and maintenance therapy. Unfortunately, strong data to support this will continue to be a challenge given the rare incidence of isolated SEIC without concurrent USC. The utility of adjuvant radiotherapy remains unclear and given its noninvasive nature and propensity for distant recurrence, may be of little utility. Regardless of the adjuvant therapies selected, routine surveillance like that of USC should be followed as recurrences are often noted greater than one year after initial surgery. Unlike other precursor lesions, SEIC behaves similarly to invasive carcinoma and ultimately should be treated as such for optimal disease control and outcomes.