Current Opinion in Oncology最新文献

Purpose of review: Antibody-drug conjugates (ADCs) are designed to carry cytotoxic payloads and deliver them to specific molecular targets within tumor cells. Several ADCs are already approved with many more in development across several disease types. In this review, we will provide an overview of the ADCs currently approved and those under investigation in solid tumors.

Recent findings: Currently there are dozens of ADCs under clinical study evaluation of a variety of solid tumors, and preliminary results are promising. Multiple ADCs have received regulatory approval in disease such as breast cancer, non-small cell lung cancer, and bladder cancer. While some are approved in biomarker selected settings with disease specific indication (e.g. breast cancer), others have been approved irrespective of biomarker expression (urothelial carcinoma) and pan-cancer indications in biomarker selected patients (HER2 3+ expression).

Summary: Cytotoxic chemotherapy has been the mainstay of systemic treatment for patients with various solid tumors. ADCs offer the advantage of carrying the cytotoxic payload onto a specific molecular receptor, thereby inducing a more selective response. Optimizing selection of target antigen, payload delivery and investigating biomarkers of response will be crucial for further expanding the therapeutic benefit of ADCs across solid tumors.

Purpose of review: The significantly improved survivorship in Hodgkin lymphoma is fraught with challenges, including persistent symptoms, secondary health complications, and socio-professional obstacles. This review highlights the need for comprehensive survivorship care plans that include detection of relapse, assessment of long-term side effects, screening for secondary cancers, psychological support, and assistance with socio-professional integration.

Recent findings: Cardiovascular diseases, secondary malignancies and other associated risks remains an important problem related to the effective treatment of patients with Hodgkin lymphoma. Furthermore, fertility concerns and endocrine disorders remain prevalent issues posttreatment. An optimal evaluation of the risks before and after treatment is essential to reduce the impact of these side effects on quality of life. Addressing the socio-professional reintegration of survivors, the concept of the 'Right to be forgotten' emerges as a critical consideration. This principle seeks to eliminate discrimination against cancer survivors in accessing financial services and aims for legislative changes to ensure that past cancer diagnosis does not unfairly affect survivors' futures. Implementation of this 'Right to be forgotten' in the legislature, is currently underway in European countries.

Summary: The focus of survivorship care has shifted towards the holistic management of these long-term outcomes. Quality of life for Hodgkin lymphoma survivors is affected by various treatment-related factors, with evidence suggesting that physical, psychological and socio-professional domains remain impacted years after treatment.

Purpose of review: There is significant need to improve diagnostic and therapeutic options for patients with cancer of unknown primary (CUP). In this review, we discuss the evolving landscape of molecular profiling in CUP.

Recent findings: Molecular profiling is becoming accepted into the diagnostic work-up of CUP patients with tumour mutation profiling now described in international CUP guidelines. Although tissue-of-origin (ToO) molecular tests utilising gene-expression and DNA methylation have existed some time, their clinical benefit remains unclear. Novel technologies utilising whole genome sequencing and machine learning algorithms are showing promise in determining ToO, however further research is required prior to clinical application. A recent international clinical trial found patients treated with molecularly-guided therapy based on comprehensive-panel DNA sequencing had improved progression-free survival compared to chemotherapy alone, confirming utility of performing genomic profiling early in the patient journey. Small phase 2 trials have demonstrated that some CUP patients are responsive to immunotherapy, but the best way to select patients for treatment is not clear.

Summary: Management of CUP requires a multifaceted approach incorporating clinical, histopathological, radiological and molecular sequencing results to assist with identifying the likely ToO and clinically actionable genomic alternations. Rapidly identifying a subset of CUP patients who are likely to benefit from site specific therapy, targeted therapy and/or immunotherapy will improve patient outcomes.

Purpose of review: Endometrial cancer is the most common gynecologic malignancy and sentinel lymphnode biopsy is accepted as a valid alternative to lymphadenectomy for staging purposes. Recently, sentinel node biopsy has been also extended to high-risk disease where risk of nodal involvement is higher.

Recent findings: Our review focuses on the definition of high-risk disease and how there are different concepts of high-risk in the scientific community. While the sensitivity of sentinel node biopsy has been established and accepted in lower risk endometrial cancers, only in recent years retrospective and prospective evidence has been published. Ultrastaging allows to identify more nodal disease that would normally be overlooked by traditional staging, allowing proper adjuvant therapy to be administered. The longstanding question of whether lymphadenectomy in high-risk settings is a therapeutic or a staging procedure remains open. Retrospective data, however, show that oncologic outcomes are not compromised by sentinel node biopsy.

Summary: Sentinel node biopsy is a valid alternative to traditional, more extensive nodal staging: with the addition of ultrastaging, it has more sensitivity than lymphadenectomy with less surgical morbidity. Ongoing trials will definitively establish if oncological outcomes are affected by sentinel node biopsy, but retrospective data are encouraging.

Purpose of review: In the past decade, sentinel lymph node (SLN) mapping has progressively substituted full lymphadenectomies in gynecologic oncology. In this article, we review the most relevant and the latest literature on this topic.

Recent findings: In endometrial and cervical cancer, the current evidence further support the value of indocyanine green (ICG) as tracer of choice for SLN mapping. Experience in vulvar cancer is more limited, with ICG used together with technetium-99 m (Tc-99m) as a dual tracer but ICG, so far, has not been a game changer in this setting as it has been for cervical and endometrial cancer.

Summary: For most gynecologic cancers, ICG fluorescence imaging is considered now a days the tracer of choice for lymphatic mapping. However, in early-stage vulvar cancer, SLN biopsy with radioactive tracer continues to be the standard-of-care in lymph node status assessment.

Purpose of review: The most common surgical procedure associated with lymphedema formation is the regional lymphadenectomy. One of the advantages of sentinel node biopsy is the reduction of the risk of lymphedema formation. The purpose of this review is to collect and analyze the most relevant and recent evidence of the use of sentinel node biopsy and its implication on the development of postoperative lymphedema in gynecological cancer.

Recent findings: The current evidence of the use of sentinel node biopsy in cervical cancer to reduce lymphedema is heterogeneous and more data is needed to establish its role.Sentinel lymph node biopsy in endometrial cancer is a staging procedure with lower surgical complications, as well as lymphedema formation; while the results of prospective trials evaluating its impact on quality of life are still lacking.Sentinel lymph node biopsy in vulvar cancer minimizes the need for extensive dissection and reduces the incidence of complications associated with overharvesting of lymph nodes such as lymphedema without compromising oncological outcomes.

Summary: The prevalence of lymphedema in gynecological cancer varies based on the surgical treatment or additional therapies applied. Over the past years, one of the most important surgical modifications to decrease lymphedema formation has been implementation of sentinel lymph node technique mainly in vulvar cancer patients.

Purpose of review: The rationale on the use of sentinel lymph node (SLN) biopsy in the surgical staging of apparent early-stage ovarian cancer (OC) is supported by the fact that diagnostic and prognostic role of systematic staging lymphadenectomy has been determined but its therapeutic significance is still matter of controversy. Moreover, SLN biopsy represents an option to decrease intra- and postoperative morbidity. The present review aims to provide an overview on the current and future role of SLN in OC.

Recent findings: Most recent evidence shows that the overall mean per patient SLN detection rate in case of indocyanine green (ICG) alone was 58.6% compared with 95% in case of ICG + technetium, and with 52.9% in case of technetium alone or in combination with blue dye ( P  < 0.001). Site of injection has been reported to be in both ovarian ligaments in majority of studies (utero-ovarian ligament and infundibulo-pelvic ligament), before or after ovarian mass removal, at time of primary or re-staging surgery and by minimally invasive or open approach. Cervical injection has been recently proposed to replace utero-ovarian injection. SLN detection rate in patients with confirmed ovarian malignancy varied across different studies ranging between 9.1% and 91.3% for the injection in the utero-ovarian ligament and migration to pelvic lymph nodes and between 27.3% and 100% for the injection in the infundibulo-pelvic ligament and migration to para-aortic lymph nodes. No intra- or postoperative complication could be attributed directly to SLN biopsy. The sensitivity and the accuracy of SLN in detecting lymphatic metastasis ranged between 73.3-100% and 96-100%, respectively. In up to 40% of positive SLNs, largest metastatic deposit was classified as micro-metastasis or isolated tumor cells, which would have been missed without ultrastaging protocol.

Summary: SLN biopsy represents a promising tool to assess lymph node status in apparent early-stage OC. The type and volume of injected tracer need to be considered as appear to affect SLN detection rate. Ultrastaging protocol is essential to detect low volume metastasis. Sensitivity and accuracy of SLN biopsy are encouraging, providing tracer injection in both uterine and ovarian ligaments.

Purpose of review: This review underscores the critical role and challenges associated with the widespread adoption of artificial intelligence in cancer care to enhance disease management, streamline clinical processes, optimize data retrieval of health information, and generate and synthesize evidence.

Recent findings: Advancements in artificial intelligence models and the development of digital biomarkers and diagnostics are applicable across the cancer continuum from early detection to survivorship care. Additionally, generative artificial intelligence has promised to streamline clinical documentation and patient communications, generate structured data for clinical trial matching, automate cancer registries, and facilitate advanced clinical decision support. Widespread adoption of artificial intelligence has been slow because of concerns about data diversity and data shift, model reliability and algorithm bias, legal oversight, and high information technology and infrastructure costs.

Summary: Artificial intelligence models have significant potential to transform cancer care. Efforts are underway to deploy artificial intelligence models in the cancer practice, evaluate their clinical impact, and enhance their fairness and explainability. Standardized guidelines for the ethical integration of artificial intelligence models in cancer care pathways and clinical operations are needed. Clear governance and oversight will be necessary to gain trust in artificial intelligence-assisted cancer care by clinicians, scientists, and patients.

Purpose of review: Sentinel lymph node biopsy (SLNB) is a widely used technique in other gynaecological tumours but has not yet been implemented as the gold standard technique for nodal staging in cervical cancer. Since the majority of evidence is derived from retrospective studies, this review aims to summarize the most recent evidence on this relevant topic.

Recent findings: SLNB has demonstrated to be a well tolerated technique for lymph node staging in early-stage cervical cancer patients with promising future as exclusive lymph node assessment method avoiding full lymphadenectomy. Moreover, it allows ultrastaging and unfrequent drainage identification, which enables the detection of patients at a high risk of recurrence who would otherwise remain unnoticed. When compared with pelvic lymphadenectomy, SLNB is also associated with less intraoperative and postoperative complications, especially in terms of lymphedema formation.

Summary: The available evidence suggests that SLNB offers numerous advantages over the standard pelvic lymphadenectomy reducing morbidity rates and increasing diagnostic accuracy. Three ongoing prospective trials will likely answer the controversies over these questions.

Purpose of review: Hodgkin lymphoma (HL) occurs at two age peaks around 25 and 60 years of age. Due to varying fitness and co-morbidities older patients are a heterogeneous group that has relatively poor treatment outcomes. The evolving therapeutic landscape for older HL is summarized herein.

Recent findings: Due to lack of data from larger trials and approval of novel drugs, first-line treatment of limited-stage HL (i.e. early-stage favourable and unfavourable) remains largely A(B)VD and radiotherapy based. For patients with advanced-stage HL, the anti-CD30 antibody-drug conjugate brentuximab vedotin is approved in combination with AVD chemotherapy (BV-AVD). Due to toxicities such as febrile neutropenia or polyneuropathy and lack of improvement in progression-free and overall survival in the older subgroup, fully concomitant BV-AVD is however not used widely. More recently, promising early data was reported with the combination of nivolumab and AVD (N-AVD) in patients >60 years with advanced-stage HL. Second-line treatment depends on fitness and might include high-dose chemotherapy and autologous stem-cell transplantation for selected patients. For unfit or multiply relapsed patients, anti-PD1 antibodies are the preferred treatment option.

Summary: The increasing number of older HL patients constitutes a therapeutic challenge despite recent advances and the increased usage of targeted agents.