Emerging pharmacotherapy trends in preventing and managing oral mucositis induced by chemoradiotherapy and targeted agents.

INTRODUCTION: The introduction of targeted therapy and immunotherapy has tremendously changed the clinical outcomes and prognosis of cancer patients. Despite innovative pharmacological therapies and improved radiotherapy (RT) techniques, patients continue to suffer from side effects, of which oral mucositis (OM) is still the most impactful, especially for quality of life. AREAS COVERED: We provide an overview of current advances in cancer pharmacotherapy and RT, in relation to their potential to cause OM, and of the less explored and more recent literature reports related to the best management of OM. We have analyzed natural/antioxidant agents, probiotics, mucosal protectants and healing coadjuvants, pharmacotherapies, immunomodulatory and anticancer agents, photobiomodulation and the impact of technology. EXPERT OPINION: The discovery of more precise pathophysiologic mechanisms of CT and RT-induced OM has outlined that OM has a multifactorial origin, including direct effects, oxidative damage, upregulation of immunologic factors, and effects on oral flora. A persistent upregulated immune response, associated with factors related to patients' characteristics, may contribute to more severe and long-lasting OM. The goal is strategies to conjugate individual patient, disease, and therapy-related factors to guide OM prevention or treatment. Despite further high-quality research is warranted, the issue of prevention is paramount in future strategies.

Joint EANM-SNMMI guideline on the role of 2-[18F]FDG PET/CT in no special type breast cancer : (endorsed by the ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA).

INTRODUCTION: There is much literature about the role of 2-[18F]FDG PET/CT in patients with breast cancer (BC). However, there exists no international guideline with involvement of the nuclear medicine societies about this subject. PURPOSE: To provide an organized, international, state-of-the-art, and multidisciplinary guideline, led by experts of two nuclear medicine societies (EANM and SNMMI) and representation of important societies in the field of BC (ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA). METHODS: Literature review and expert discussion were performed with the aim of collecting updated information regarding the role of 2-[18F]FDG PET/CT in patients with no special type (NST) BC and summarizing its indications according to scientific evidence. Recommendations were scored according to the National Institute for Health and Care Excellence (NICE) criteria. RESULTS: Quantitative PET features (SUV, MTV, TLG) are valuable prognostic parameters. In baseline staging, 2-[18F]FDG PET/CT plays a role from stage IIB through stage IV. When assessing response to therapy, 2-[18F]FDG PET/CT should be performed on certified scanners, and reported either according to PERCIST, EORTC PET, or EANM immunotherapy response criteria, as appropriate. 2-[18F]FDG PET/CT may be useful to assess early metabolic response, particularly in non-metastatic triple-negative and HER2+ tumours. 2-[18F]FDG PET/CT is useful to detect the site and extent of recurrence when conventional imaging methods are equivocal and when there is clinical and/or laboratorial suspicion of relapse. Recent developments are promising. CONCLUSION: 2-[18F]FDG PET/CT is extremely useful in BC management, as supported by extensive evidence of its utility compared to other imaging modalities in several clinical scenarios.

Fulfilling the Role of a Parent While Undergoing Treatment for Cancer: A Review of the Literature and the Potential Impact of Childcare Support on Cancer Outcomes.

Breast cancer is the most prevalent malignancy among adolescents and young adults (AYAs). Despite the efficacy of chemotherapy, AYA patients contend with psychosocial challenges, including psychological distress and financial toxicity, exacerbated further by those with dependent children. Parenting responsibilities intersect with cancer care, impacting both family dynamics and treatment adherence. Despite recognized needs, however, the impact of parenting concerns or even parenting status and the presence of dependents has not been systematically addressed and there is a paucity of interventional research regarding patients with cancer as concomitant caregivers. A feasibility study conducted by the Brown University Oncology Cooperative Group demonstrated the potential benefits of providing financial assistance for childcare, both improving treatment adherence and reducing distress among participants. Similar interventions have shown promise in addressing financial hardships for AYA patients with cancer who are concomitant caregivers. Ultimately, parenting concerns have a significant impact on medical decision-making, and further interventional research on childcare support is required to examine the ways in which health systems can improve family stability, stress, and quality of life.

The Genomic, Transcriptomic, and Immunologic Landscape of HRAS Mutations in Solid Tumors.

Tipifarnib is the only targeted therapy breakthrough for HRAS-mutant (HRASmt) recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The molecular profiles of HRASmt cancers are difficult to explore given the low frequency of HRASmt. This study aims to understand the molecular co-alterations, immune profiles, and clinical outcomes of 524 HRASmt solid tumors including urothelial carcinoma (UC), breast cancer (BC), non-small-cell lung cancer (NSCLC), melanoma, and HNSCC. HRASmt was most common in UC (3.0%), followed by HNSCC (2.82%), melanoma (1.05%), BC (0.45%), and NSCLC (0.44%). HRASmt was absent in Her2+ BC regardless of hormone receptor status. HRASmt was more frequently associated with squamous compared to non-squamous NSCLC (60% vs. 40% in HRASwt, p = 0.002). The tumor microenvironment (TME) of HRASmt demonstrated increased M1 macrophages in triple-negative BC (TNBC), HNSCC, squamous NSCLC, and UC; increased M2 macrophages in TNBC; and increased CD8+ T-cells in HNSCC (all p < 0.05). Finally, HRASmt was associated with shorter overall survival in HNSCC (HR: 1.564, CI: 1.16-2.11, p = 0.003) but not in the other cancer types examined. In conclusion, this study provides new insights into the unique molecular profiles of HRASmt tumors that may help to identify new targets and guide future clinical trial design.

Tissue-specific thresholds of mutation burden associated with anti-PD-1/L1 therapy benefit and prognosis in microsatellite-stable cancers.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 or its ligand (PD-1/L1) have expanded the treatment landscape against cancers but are effective in only a subset of patients. Tumor mutation burden (TMB) is postulated to be a generic determinant of ICI-dependent tumor rejection. Here we describe the association between TMB and survival outcomes among microsatellite-stable cancers in a real-world clinicogenomic cohort consisting of 70,698 patients distributed across 27 histologies. TMB was associated with survival benefit or detriment depending on tissue and treatment context, with eight cancer types demonstrating a specific association between TMB and improved outcomes upon treatment with anti-PD-1/L1 therapies. Survival benefits were noted over a broad range of TMB cutoffs across cancer types, and a dose-dependent relationship between TMB and outcomes was observed in a subset of cancers. These results have implications for the use of cancer-agnostic and universal TMB cutoffs to guide the use of anti-PD-1/L1 therapies, and they underline the importance of tissue context in the development of ICI biomarkers.

Exploring DESTINY: the Past, Present, and Future of Trastuzumab Deruxtecan.

PURPOSE OF REVIEW: HER2-positive breast cancer accounts for 10-15% of all breast cancers and fam-trastuzumab deruxtecan (T-DXd) has played a major role in moving the treatment of HER2-expressing disease forward. RECENT FINDINGS: T-DXd is a novel antibody-drug conjugate (ADC) composed of a humanized IgG1 monoclonal antibody against HER2 receptor bound to a potent topoisomerase I cytotoxin payload by a cleavable peptide linker. It has been shown to have robust preclinical activity in pretreated cancer cell lines, as well as meaningful clinical activity in advanced HER2-expressing breast cancer. Recent studies have demonstrated T-DXd as an active agent for metastatic HER2-positive patients, and as a viable additional line for heavily pretreated patients with HER2-low disease. The toxicity of T-DXd remains manageable and burden of side effects seems to be lower when offered as an earlier line of therapy over the course of treatment. In this review, we discuss the pharmacology of T-DXd, review pertinent preclinical and clinical data, and address potential challenges and future directions related to the use of T-DXd in clinical practice.

Evaluating Patient Experience in a Multidisciplinary Breast Cancer Clinic: A Prospective Study.

Background: Multidisciplinary clinics (MDCs) are a care model in which patients see several physicians across specialties and/or other allied health professionals in a single appointment in a shared space. This study sought to better understand patients' experiences with breast cancer (BC) MDC. Methods: A total of 429 patients diagnosed with BC and seen in a MDC between November 2020 and November 2021 were invited to participate in a patient experience survey. Results: In total, 116 patient respondents (27%) with representative demographics described their experience. Most patients report feeling "somewhat prepared" for the BC MDC experience (67%, median = 3.7, interquartile range [IQR] = 1.9), but with variability. The major areas of positive feedback were that the MDC was convenient (89.3%), efficient use of time (65.2%), and a good way to get questions answered (65.2%). Major criticisms included that the MDC was overwhelming (16.1%) and/or too long (4.5%). When asked to rate the top three satisfaction areas of MDCs, patients chose seeing multiple providers during a single visit (80.4%), communication about the process before and throughout the MDC (48.2%), and inclusivity of their support system (38.4%). The highest rated dissatisfiers were the volume of information presented (42.9%) and patients' emotional comfort (anxiety/stress) during MDC appointment (30.2%). Overall, 83% of patients with BC rate the MDC experience as excellent (median = 4.8, IQR = 0.9) and would be "very likely" to recommend BC MDC (median = 4.8, IQR = 0.9). Conclusion: Patients value seeing multiple providers simultaneously in an environment inclusive of their support systems, which is described as convenient and efficient. Improving emotional distress is a key opportunity to improve patient experience.

Sequencing Antibody Drug Conjugates in Breast Cancer: Exploring Future Roles.

Antibody drug conjugates (ADCs) have emerged as a highly effective treatment strategy across breast cancer (BC) subtypes, including human epidermal growth factor receptor 2-positive (HER2+), hormone-receptor positive (ER/PR+), and triple-negative breast cancer (TNBC). Over the past twenty years, ADCs have undergone relevant evolutions, from target diversity to payload ratio, to linker design, allowing for a progressive increase in their efficacy. From the first-generation ADC, trastuzumab emtansine (T-DM1), approved in 2013 for HER2+ breast cancer, to next generation ADCs such as sacituzumab govitecan and trastuzumab deruxtecan, to emerging ADCs on the horizon, we continue to see unparalleled efficacy compared to traditional chemotherapy. However, each ADC has brought a new cadre of adverse events for clinicians and patients to manage. Importantly, with the development and approval of several ADCs to treat metastatic breast cancer, there are unanswered clinical questions surrounding how to optimally sequence treatment for patients who may be candidates for more than one ADC and, in general, how to treat patients beyond progression on ADCs. From bench to bedside, in this review, we will discuss the pharmacology and current indications for the novel ADCs trastuzumab deruxtecan and sacituzumab govitecan. Highlighting emerging ADCs and ongoing clinical trials, we will anticipate the changes in the breast cancer treatment paradigm. Lastly, we will outline the available data and current approaches for adverse event management and sequencing strategies for ADCs in clinical practice, including proposed mechanisms of resistance.

The Careers and Professional Well-Being of Women Oncologists During the COVID-19 Pandemic: Responding for Tomorrow.

The COVID-19 pandemic exacerbated gender inequity in medicine, with women physicians reporting greater household responsibilities than their men counterparts and steeper barriers to career advancement. The pandemic highlighted the systemic assumptions and challenges faced by women physicians, which we anticipate is also true in our field of oncology. Prior literature suggests that women physicians were tasked with increased personal and professional responsibilities without compensation for their additional work, as well as derailments in career progression and significant burnout. Our aims are to highlight areas of opportunity to optimize the workplace experience of the oncology workforce and to invest in the professional well-being and sustainability of women oncologists as a step toward global workplace equity and future pandemic preparedness.

Sequencing systemic therapy in hormone-receptor positive metastatic breast cancer: a modern paradigm.

Deaths from metastatic breast cancer continue to be a leading cause of global cancer mortality among women. The pace of advances in the treatment of hormone-receptor positive metastatic breast cancer (HR+ MBC) has introduced nuance and complexity in choosing between available agents as patients and physicians explore options across lines of therapy. In this review, we explore the modern paradigm of treatment options and the sequential approach to HR+ MBC, as well as treatment options on the horizon, and the particular impact on survival outcomes and the associated adverse effects of those treatments. We discuss the diagnostic approach, first- and second-line management, as well as management of later-line endocrine-refractory HR+ MBC. Treatments discussed include cyclin-dependent kinase 4/6 inhibitors, antibody drug conjugates, and targeted therapies against phosphatidylinositol-4,5-bisphosphate-3-kinase catalytic subunit alpha (PIK3CA), estrogen receptor 1 (ESR1), and poly[ADP-ribose] polymerase (PARP), among others. Building from the initial diagnostic approach, we describe how to pragmatically layer options by appropriate line of therapy and personalized drivers of disease to aid in treatment decision making step-by-step. Combining sequential treatment options, evolving treatment options, and advanced genetic and genomic testing along with shared decision making between patients and physicians, this review aims to outline the key factors that ultimately drive the decisions for treatment in hormone-positive metastatic breast cancer.

Newly Approved and Emerging Agents in HER2-Positive Metastatic Breast Cancer.

Human epidermal growth factor receptor 2-positive breast cancer (HER2+ BC) is an aggressive tumor type, accounting for 15% to 20% of the approximately 300,000 new BC cases in the United States each year. The goal of this review is to discuss the evolving landscape of therapies for HER2+ metastatic BC (mBC). Targeted therapies that have been the standard of care (SOC) for HER2+ mBC for almost a decade have greatly improved patient outcomes. The SOC for the first-line treatment of HER2+ mBC continues to be HER2-targeted monoclonal antibodies (mAbs) + a taxane, but recent updates in the second-line setting favor use of a newer HER2-targeted antibody-drug conjugate (ADC), trastuzumab deruxtecan, versus the prior SOC ADC, trastuzumab emtansine. Numerous options are now available in the third line and beyond, including tyrosine kinase inhibitor (TKI) regimens, newer mAbs, and other ADCs. The optimal course of treatment for individual patients can be guided by location of metastases, prior therapies, concomitant biomarkers, and monitoring and management of adverse events. Ongoing trials will further the evolution of the HER2+ mBC treatment landscape. Furthermore, next-generation ADCs, TKIs, and classes of drugs that have not been approved for the treatment of HER2+ mBC, including immune checkpoint inhibitors and cyclin-dependent kinase 4 and 6 inhibitors, are also being evaluated for their efficacy in the first and second line. Although the influx of new drugs may complicate treatment decisions for physicians, having a multitude of options will undoubtedly further improve patient outcomes and patient-centered care.

Triple-negative Breast Carcinoma With Apocrine and Histiocytoid Features: A Clinicopathologic and Molecular Study of 18 Cases.

Triple-negative breast cancer (TNBC) is a heterogenous group of tumors. Most TNBCs are high-grade aggressive tumors, but a minority of TNBCs are not high grade, with relatively indolent behavior and specific morphologic and molecular features. We performed a clinicopathologic and molecular assessment of 18 non-high-grade TNBCs with apocrine and/or histiocytoid features. All were grade I or II with low Ki-67 (≤20%). Thirteen (72%) showed apocrine features, and 5 (28%) showed histiocytoid and lobular features. In all, 17/18 expressed the androgen receptor, and 13/13 expressed gross cystic disease fluid protein 15. Four (22.2%) patients were treated with neoadjuvant chemotherapy, but none achieved a pathologic complete response. In all, 2/18 patients (11%) had lymph node metastasis at the time of surgery. None of the cases had a recurrence or disease-specific death, with an average follow-up time of 38 months. Thirteen cases were profiled by targeted capture-based next-generation DNA sequencing. Genomic alterations (GAs) were most significant for PI3K-PKB/Akt pathway (69%) genes, including PIK3R1 (23%), PIK3CA (38%), and PTEN (23%), and RTK-RAS pathway (62%) including FGFR4 (46%) and ERBB2 (15%). TP53 GA was seen in only 31% of patients. Our findings support those on high-grade TNBCs with apocrine and/or histiocytoid features as a clinicopathologic and genetically distinct subgroup of TNBC. They can be defined by features including tubule formation, rare mitosis, low Ki-67 (≤20%), triple-negative status, expression of androgen receptor and/or gross cystic disease fluid protein 15, and GA in the PI3K-PKB/Akt and/or RTK-RAS pathway. These tumors are not sensitive to chemotherapy but have favorable clinical behavior. Tumor subtype definitions are the first step to implementing future trial designs to select these patients.

PET/CT in Patients with Breast Cancer Treated with Immunotherapy.

Significant advances in breast cancer (BC) treatment have been made in the last decade, including the use of immunotherapy and, in particular, immune checkpoint inhibitors that have been shown to improve the survival of patients with triple negative BC. This narrative review summarizes the studies supporting the use of immunotherapy in BC. Furthermore, the usefulness of 2-deoxy-2-[18F]fluoro-D-glucose (2-[18F]FDG) positron emission/computerized tomography (PET/CT) to image the tumor heterogeneity and to assess treatment response is explored, including the different criteria to interpret 2-[18F]FDG PET/CT imaging. The concept of immuno-PET is also described, by explaining the advantages of mapping treatment targets with a non-invasive and whole-body tool. Several radiopharmaceuticals in the preclinical phase are referred too, and, considering their promising results, translation to human studies is needed to support their use in clinical practice. Overall, this is an evolving field in BC treatment, despite PET imaging developments, the future trends also include expanding immunotherapy to early-stage BC and using other biomarkers.

Frequency, barriers, outcomes, and consequences of reporting sexual harassment in clinical oncology.

Sexual harassment is increasingly recognized as widely prevalent in medicine. Broad efforts at the organizational and society level are working to address this inequity, but many of these efforts rely on reporting to eradicate problematic behaviors and shift culture. We examined, among oncologists experiencing sexual harassment, the frequency of reporting, as well as barriers, outcomes, and consequences of reporting. Among 271 survey respondents, 217 reported sexual harassment from peers or superiors or from patients or families. Most harassed oncologists (n = 148, 68%) did not report the event to authority because of concerns about future negative consequences for themselves. Among the minority who reported harassment (n = 31, 14%), 52% felt their concerns were not taken seriously and 55% reported no action was taken as a result of their report. Furthermore, 52% experienced retaliatory behavior. Addressing these findings may help to inform the change necessary to create an antiharassment culture in oncology.

Social Media and Professional Development for Oncology Professionals.

The use of social media continues to increase in health care and academia. Health care practice, particularly the oncologic field, is constantly changing because of new knowledge, evidence-based research, clinical trials, and government policies. Therefore, oncology trainees and professionals continue to strive to stay up-to-date with practice guidelines, research, and skills. Although social media as an educational and professional development tool is no longer completely new to medicine and has been embraced, it is still under-researched in terms of various outcomes. Social media plays several key roles in professional development and academic advancement. We reviewed the literature to evaluate how social media can be used for professional development and academic promotion of oncology professionals.

The Rise of the Expert Patient in Cancer: From Backseat Passenger to Co-navigator.

PURPOSE: Patients who have cancer have leveraged the Internet to gain a better understanding of their disease and connect across geographic boundaries with others facing the same challenges. Online cancer communities have developed into resources that highlight new research and evolving care pathways. Combined with increasing health literacy and social media, they have enabled some patients to become experts in their cancer. This combination of empowerment and expertise describes the new "e-patients." METHODS: We reviewed the literature to identify key areas where expert e-patients have directly participated in advancing cancer medicine, as well as opportunities available to those who wish to become more involved in research advocacy. RESULTS: E-patients are widely acknowledged as key stakeholders in oncology by clinicians, researchers, cancer centers, government agencies, and nonprofits. Their input is vital for informing cancer care delivery, developing and launching research initiatives, creating care guidelines and pathways, and formulating policy. CONCLUSION: Expert e-patients play an expanded role in their own care and in larger conversations regarding practice, research, and policy. Clinicians can engage e-patients as partners in cancer care as we work together towards improving health care access and outcomes for people with cancer.