Current Treatment Options in Oncology最新文献

Opinion statement: Palliative care seeks to address the physical, psychosocial and spiritual concerns of patients with a life limiting illness and their caregivers. Early referral to palliative care improves symptoms and is the standard of care. This paper evaluates the evidence for different models of community palliative care and looks at the effects of homecare, hospice programs and residential aged care facility (RACF) interventions on symptom management, home death rate and acute health service utilization. It also examines the impact of COVID-19, telehealth, integration and staffing models on the efficacy of community palliative care. Evidence suggests that community palliative care increases the rate of death at home and may improve satisfaction with care, but effect on symptoms and acute health care utilization are less certain. Enrolment in a hospice program may decrease hospitalizations and improve satisfaction. RACF staff training interventions to improve the quality of palliative care provided to residents show mixed results across all indicators. COVID-19 saw a relative increase in the demand for community palliative care, as people opted out of the hospital system. Models of community palliative care that facilitate integration, support primary health providers, and promote technological innovation are worthy of further research.

Opinion statement: The therapeutic landscape for HER2-positive metastatic breast cancer has exploded in the last two decades following the initial advent of trastuzumab, a monoclonal antibody. While the first line treatment has remained a combination of dual HER2 blockade with taxane chemotherapy, we now have several exciting options in the second line and beyond. The introduction of antibody-drug conjugates, in specific trastuzumab deruxtecan, has resulted in the best progression-free survival among patients with this subtype of breast cancer. Given the excellent outcomes of these drugs, clinical trials are now evaluating the role of ADCs in the front-line setting in previously untreated patients. In addition, there are also clinical trials evaluating the role of other targets in patients with HER2-positive cancers, including PI3KCA mutations, PD-L1 and CDK4/6. Given the predilection for brain metastases in this population, there is enthusiasm to identify the optimal combination of effective treatments. Tucatinib, capecitabine, and trastuzumab combination represent one such promising strategy. With the increasing longevity of these patients, important clinical questions include optimal treatment sequencing, the role of de-escalation of treatment in excellent responders, and the associated financial toxicity. Despite the aggressive nature of this subtype of breast cancer, the outcomes continue to improve for these patients with the evolving treatments.

Opinion statement: Parenchymal liver metastases from ovarian cancer, occurring in 2-12.5% of cases, significantly worsen prognosis. While surgery and systemic treatments remain primary options, unresectable or chemotherapy-resistant multiple liver metastases pose a significant challenge. Recent advances in liver-directed therapies, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization (TACE), and radioembolization, offer potential treatment alternatives. However, the efficacy of these techniques is limited by factors such as tumor size, number, and location. The ideal candidate for tumor ablation is a patient with paucifocal disease, a single tumor up to 5 cm or up to 3 tumors smaller than 3 cm and tumors 1 cm away from major bile ducts and high-flow vessels. Transarterial chemoembolization could be performed in patients with less than 70% tumor load. Differently, radioembolization is available with less limitation on the sites or number of liver cancers. Radioembolization techniques are also able to downsize liver metastases. However, there are limited data regarding the outcomes of loco-regional therapy in patients with hepatic metastases from ovarian cancer. Advancing liver-directed therapies through interventional oncology, combined with robust data on the oncological efficacy of these local treatments, will validate their potential as effective locoregional therapies for liver metastases. This could offer a promising treatment option for patients with ovarian cancer and unresectable hepatic metastases.

Opinion statement: The renin-angiotensin-aldosterone system (RAAS) is a crucial regulator of the cardiovascular system and a target for widely used therapeutic drugs. Dysregulation of RAAS, implicated in prevalent diseases like hypertension and heart failure, has recently gained attention in oncological contexts due to its role in tumor biology and cardiovascular toxicities (CVTs). Thus, RAAS inhibitors (RAASi) may be used as potential supplementary therapies in cancer treatment and CVT prevention. Oncological treatments have evolved significantly, impacting patient survival and safety profiles. However, they pose cardiovascular risks, necessitating strategies for mitigating adverse effects. The main drug classes used in oncology include anthracyclines, anti-HER2 therapies, immune checkpoint inhibitors (ICIs), and vascular endothelial growth factor (VEGF) signaling pathway inhibitors (VSPI). While effective against cancer, these drugs induce varying CVTs. RAASi adjunctive therapy shows promise in enhancing clinical outcomes and protecting the cardiovascular system. Understanding RAAS involvement in cancer and CVT can inform personalized treatment approaches and improve patient care.

Opinion statement: Breast cancer does not wait until a woman reaches her 50's to strike. One in six cases occurs in women between the ages of 40 and 49 and breast cancer is the most prevalent cancer and the leading cause of cancer-related deaths among women under 50 in the United States (10% of breast cancer deaths), emphasizing the urgency of early detection (American Society. 2024). Duffy et al. highlight the vital role of mammography screening in younger women, showing that starting screening at 40 reduces breast cancer mortality, with a consistent absolute reduction over time (Duffy et al. Health Technol Assess. 24(55):1-24, 2020). By starting yearly mammograms at 40, we could see a remarkable 40% reduction in breast cancer deaths (Monticciolo et al. J Am Coll Radiol. 18(9):1280-8, 2021). Screening at age 40 also adds little to the burden of overdiagnosis that already arises from screening at age 50 and older. Comparing this to biennial screening between ages 50-74, yearly screening at 40 saves approximately 13,770 more lives annually according to a report by the American Cancer Society published in JAMA in 2015 (Oeffinger et al. JAMA. 314(15):1599-614, 2015). But it's not just about saving lives; it's also about preserving quality of life. Between ages 40 and 49, 12-15% of years of life lost are attributed to breast cancer, highlighting the impact on women's lives. Early detection through screening can minimize these losses, ensuring more years spent with loved ones. It's clear: starting mammograms at age 40 saves lives. We must prioritize early detection and make screening accessible to all women, regardless of age. This proactive approach can reduce the burden of breast cancer and pave the way for a healthier future for women everywhere.

Opinion statement: Mutations in isocitrate dehydrogenase-1 (IDH1) are recurrent in several malignancies and prevalent in acute myeloid leukemia (AML). Olutasidenib and ivosidenib are inhibitors that target mutant IDH1 (mIDH1) and are FDA approved for the treatment of patients with mIDH1 AML. Olutasidenib and ivosidenib were identified through unique molecular screens and thus are structurally very different molecules. A difference in clinical outcomes has been observed with olutasidenib, which has a longer duration of response than ivosidenib, despite similar rates of response being achieved with the two drugs, such as complete remission (CR) or CR with partial hematologic recovery (CR/CRh). In the absence of a head-to-head trial, this review examines both the extent of differences in clinical outcomes with the two drugs and provides the first comparison of the unique molecular and mechanistic features of each drug, such as molecular structure and binding kinetics, that may contribute to the observed clinical difference in outcomes. Olutasidenib is structurally smaller with a lower molecular weight than ivosidenib (FW 355 vs FW 583) and thus occupies less space in the binding pocket of IDH1 dimers, making it resistant to displacement by IDH1 second-site mutations. In biochemical studies, olutasidenib selectively inhibits mutant but not wild-type IDH1, whereas ivosidenib appears to potently block both mutant and wild-type IDH1. Although they have the same target, olutasidenib and ivosidenib have unique molecular features, which may translate to selectivity differences in their inhibitory activity against IDH1.

Opinion statement: Rectal neuroendocrine neoplasms (NENs) are increasing in incidence. Most lesions are low grade, well-differentiated neuroendocrine tumours with good long term outcomes. However there is metastatic potential and resection offers the only option for a cure and in most cases should be offered to reduce the risk of metastases. Careful staging of rectal NENs should be performed prior to consideration of resection in order to ensure the appropriate technique is chosen, and reduce the risk of incomplete resection. Resection can be endoscopic or surgical, and selecting the appropriate resection technique relies on tumour characteristics such as size, grade, invasion into the muscularis propria, presence of lymph node involvement or of distal metastases. Some patients may require systemic therapies which may involve somatostatin analogues (SSAs), everolimus, tyrosine kinase inhibitors (TKIs), chemotherapy or peptide receptor radionuclide therapy (PRRT). Due the rarity of these tumours, much of the evidence is based on retrospective reviews or smaller cohort studies. This article is an update of the current evidence available to guide management.

Opinion statement: Osteosarcoma is the most common primary malignant bone tumor in adolescents and adults. The 5-year survival rate is 65% when localized; however, survival drops dramatically to 10-20% in cases of metastatic disease. Therapy for osteosarcoma saw its first significant advancement in the 1970-80's, with the introduction of our current standard of care, consisting of the neo/adjuvant treatment regimen methotrexate, doxorubicin (Adriamycin), and cisplatin (collectively referred to as MAP) and surgical resection. Since MAP, development of a better therapeutic approach has stalled, creating a plateau in patient outcomes that has persisted for 40 years. Despite substantial research into a variety of pathways for novel treatment options, clinical trials have not produced sizeable improvements in outcomes. In this article, we discuss our current neoadjuvant standard of care therapy, followed by a review of contemporary therapeutic options, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), monoclonal antibodies (mAbs), and chimeric antigen receptor (CAR) T cells. Lastly, we consider the challenges hindering the success of novel treatment options and future research directions.

Opinion statement: Lung cancer is expected to contribute to about 0.234 million new cases and about 0.125 million mortalities in the United States in the year 2024. Small cell lung cancer (SCLC), a neuroendocrine carcinoma, has lesser prevalence but is more aggressive at an extensive stage where the tumor is not only confined to hemithorax, mediastinum, and supraclavicular region but spread beyond the supraclavicular region. The prognosis of SCLC, irrespective of the limited or extensive stage, is very poor. Only a 5-10% overall survival rate in five years is expected and with extensive-stage SCLC, long-term disease-free survival is rare. In May 2024, the USFDA approved Tarlatamab-dlle, a DLL3 targeted bi-specific T-cell engager, for treating extensive-stage SCLC in adult patients, on or after platinum-based chemotherapy or on progression. Before the approval of Tarlatamab-dlle, only a few drugs, such as Atezolizumab and Durvalumab, received FDA approval for treating extensive-stage SCLC. It might be possible that Tarlatamab-dlle received accelerated FDA approval for extensive-stage SCLC, leaving some questions unanswered at this stage. This manuscript is focused on clinical, pre-clinical, and other pharmacological aspects of Tarlatamab-dlle for extensive-stage SCLC.

Opinion statement: Multiple myeloma (MM) is a heterogeneous plasma cell tumor with a survival period of several months to over ten years. Despite the development of various new drugs, MM is still incurable and recurs repeatedly. Bortezomib, a landmark event in the history of MM treatment, has dramatically improved the prognosis of patients with MM. Although proteasome inhibitors (PIs) represented by bortezomib, have greatly prolonged MM survival, unfortunately, almost all MM will develop bortezomib resistance, leading to relapse with a shorter survival. It has been reported that both the tumor microenvironment and myeloma cells drive bortezomib resistance. Multiple treatment methods have been attempted to overcome bortezomib resistance, but unfortunately, there has been no breakthrough. It is believed that the key resistance mechanism has not yet been discovered. A deeper understanding of the mechanism of bortezomib resistance and strategies to overcome it can help identify key resistance mechanisms and further improve the prognosis of MM.