End-of-life decision making in oncology is a complex landscape, encompassing clinical, ethical, cultural, and human dimensions. It occurs at the intersection of medical possibility, ethical complexity, cultural context, and human experience. Regardless of where they reside, patients at the end of life face profound choices regarding comfort, dignity, and the meaning of hope, regardless of whether cure is no longer attainable or treatment is no longer desired. Across Africa, palliative care, in general, has expanded through community-based and integrated models, yet access, including at life's end, remains limited by resource constraints, workforce shortages, and inadequate availability of essential medicines, particularly opioids. These inequities shape what choice means in practice, often constraining patient preferences and reinforcing the need for system-level integration and culturally responsive care. By contrast, medical aid in dying in the United States reflects a growing emphasis on autonomy and control at the patient level, and it generates evolving clinical practices and ongoing ethical debate. Within the end-of-life spectrum, hope persists as a dynamic and measurable construct associated with improved quality of life and potentially survival, while remaining adaptable to changing goals in advanced illness. Nonetheless, the human dimensions of care—including psychological distress, communication, and relational continuity—are frequently underemphasized in advanced cancer and at the end of life. Addressing these gaps is essential for ensuring that patients obtain support that emphasizes meaning, agency, and dignity at the end of life.
Immunotherapy and BRAF-targeted therapy strategies reduce recurrence risk and improve survival in patients with high-risk resected and metastatic melanoma, respectively. Optimizing the use of these treatment options can maximize clinical benefit and reduce exposure to adverse events and cost and burden of care for patients. In high-risk resectable disease, neoadjuvant anti-PD-1 monotherapy and anti-PD-1/anti-CTLA-4 combination therapy demonstrate greater event-free survival compared with adjuvant therapy alone and can be used to guide de-escalation of treatment in patients with major pathologic responses or a change in therapy in patients with suboptimal responses. In patients with metastatic disease, selection of frontline anti-PD-1-based therapy can incorporate multiple factors when making decisions with patients including subtype of melanoma, extent of disease, risk of adverse events, and salvage options. While consideration of toxicity risk is important, more aggressive up-front strategies can lead to better off-treatment survival outcomes. Duration of therapy to achieve maximal benefit continues to be an area of investigation with the depth of response potentially being a key biomarker. Strategies such as post-treatment positron emission tomography/computed tomography scan for assessment of residual active disease may guide these decisions. In patients with no evidence of post-treatment active disease, shorter durations of therapy may be feasible without diminished efficacy. When active disease remains, risk for progression is heightened and continuation/escalation of treatment is warranted.
Rare head and neck cancers, including adenoid cystic carcinoma (ACC), differentiated thyroid cancer (DTC), and sinonasal/paranasal tumors, represent a diverse pathology with shared clinical challenges, including heterogenous biology and limited prospective evidence. Although these tumors may present commonly as locally aggressive disease, there is distant metastatic potential, underscoring the complexities of treatment selection. Precision medicine has broadened the landscape of treatment modalities for these rare tumors; nevertheless, there are persistent critical needs for more robust molecular predictors to refine risk stratification, enhance prognostic accuracy, and drive innovative targeted therapies. In ACC, multikinase inhibitors remain a central systemic therapy strategy; however, emerging options targeting MYB and NOTCH pathways, theranostics by prostate-specific membrane antigen‑directed radioligand therapy, and immunotherapy are providing novel alternatives of care for patients with these malignancies. In radioactive iodine‑refractory DTC, redifferentiation approaches using an antineoplastic agent for 4-6 weeks have restored I131 uptake in selected patients. Clinical trials and real-world experiences with BRAF, MEK, RET, and NTRK inhibitors have revealed that a subset of patients may benefit from this approach to delay long-term systemic therapy initiation. Molecular testing has enabled better classification of sinonasal tumors, in which multimodal therapeutic approaches have been the cornerstone, with newer biomarkers guiding the consideration of immunotherapy implementation among other alternatives. In these rare malignancies, patient-centered care, including timely access to expert multidisciplinary teams in high-volume centers, prioritization for clinical trial enrollment, and balancing options on the basis of molecular profiles, remains essential to advance the field.
Neoadjuvant and perioperative immunotherapy have redefined the treatment landscape for select patients with early-stage and locally-advanced resectable non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis combined with platinum-based chemotherapy have achieved substantially higher rates of pathologic complete response and major pathologic response than chemotherapy alone, translating into meaningful improvements in event-free survival and, in select trials, overall survival. Despite this progress, several clinically important questions remain unanswered, including the relative value of neoadjuvant versus perioperative approaches, the optimal sequencing and duration of therapy, and how best to tailor treatment according to tumor biology, host features, and risk of disease recurrence. Emerging biomarkers such as PD-L1 expression, circulating tumor DNA dynamics, and pathologic response may help refine treatment selection although their role in routine decision making is still evolving. The integration of immunotherapy into curative-intent treatment also has important multidisciplinary implications. Accurate staging, appropriate biomarker testing, thoughtful considerations for multimodal therapy integration throughout the perioperative setting, high-quality surgical resection, and careful response assessment remain essential to maximize the benefit of systemic therapy. This review summarizes the current evidence supporting neoadjuvant and perioperative immunotherapy in resectable NSCLC and discusses key biomarkers, unresolved clinical questions, and the practical implications for multidisciplinary care.
Immigrants comprise a substantial and growing proportion of the US population, yet they face profound barriers to timely, affordable, and high-quality cancer care. These barriers are shaped not only by language, culture, and health literacy but also by federal and state policies that restrict insurance coverage, deter care-seeking, and heighten fear of immigration enforcement. Undocumented immigrants, in particular, remain largely excluded from Medicaid, Medicare, and other public benefits, while many lawfully present immigrants face eligibility restrictions, including the 5-year waiting period for Medicaid coverage. Although mechanisms such as Emergency Medicaid, state-funded Medicaid-equivalent programs, disease-specific safety-net programs, and Affordable Care Act waivers can help bridge gaps in access, these protections vary widely by state and remain vulnerable to policy change. Recent immigration enforcement actions and state-level requirements to collect citizenship or immigration status information in health care settings may further discourage patients from seeking care, including for cancer symptoms or treatment-related complications. For oncology professionals, these realities create urgent ethical, clinical, and practical responsibilities. Clinicians must understand how immigration and health policy affect access to care, seek institutional guidance on responding to immigration enforcement in clinical settings, and protect patient confidentiality whenever possible. At the same time, cancer programs must strengthen culturally competent care through professional interpretation, linguistically appropriate materials, community partnerships, culturally responsive care coordination, and workforce training. Ensuring equitable cancer care for immigrant populations requires both individual clinician awareness and systems-level commitment to access, trust, dignity, and high-quality care for all patients, regardless of national origin or immigration status.
Neuroendocrine neoplasms (NENs) represent a heterogeneous group of malignancies ranging from relatively indolent well-differentiated neuroendocrine tumors (NETs) to more aggressive poorly differentiated neuroendocrine carcinomas (NECs). The advent of somatostatin receptor (SSTR)-targeting therapies, particularly radioligand therapy (RLT), has transformed the therapeutic landscape of NETs. Ongoing efforts are aimed at maximizing the therapeutic benefit of RLT and include retreatment and combination strategies as well as novel α-emitter-based radiopharmaceuticals. The increasing use of molecular profiling has led to the identification of recurrent canonical alterations in pancreatic NETs, including in MEN1, ATRX/DAXX, PI3K/Akt/mTOR, and angiogenic signaling pathways, facilitating the development of effective targeted therapies. However, despite the addition of newer targeted therapies to the therapeutic armamentarium, resistance remains inevitable and highlights the need for improved predictive markers to inform therapy sequencing and novel biomarker-selected therapies. In addition, the development of novel therapeutic strategies including SSTR antagonists, nonpeptide drug conjugates, and novel radiopharmaceutical constructs highlights the potential of biomarker-informed therapies in this space. By contrast, treatment options for NECs remain limited, with modest therapeutic benefit of platinum-based chemotherapy. The identification of delta-like ligand 3 (DLL3) as a therapeutic target in high-grade NENs has led to the development of novel targeted therapies such as T-cell engagers, which have demonstrated promising activity in early phase clinical trials. In addition, other DLL3-targeting agents such as antibody-drug conjugates, trispecific engagers, and cellular therapies remain under investigation. Collectively, these advances underscore the potential of biomarker-informed treatment approaches to personalize treatment decisions and improve long-term outcomes across the NEN spectrum.
Oncology-trained physicians-including medical oncologists, radiation oncologists, and surgical oncologists-can pursue a diverse set of career paths. However, with increasing concerns about physicians moving away from the path of academic oncology, it is critical that those in academia feel supported. Career growth, promotion, and satisfaction depend upon finding a work environment that can foster development, but at the same time, individual physicians must know how to organize their goals to best advocate for their needs and set themselves up for success. In this manuscript, we review key factors and different tools that physicians can use to help shape their career through its multiple phases within academic oncology. Although each physician's career trajectory is unique, academic oncology consists of several core career niches. Across these niches, there are key domains for success including the development of clinical expertise, skill development, scholarship and grantsmanship, professional development (mentorship, committee work and national society participation, and leadership), and time management. Career development plans (CDP) are one valuable tool to help organize short- and long-term goals within these key domains. Best optimized with the assistance of a mentorship network, CDPs should continue to be updated as careers evolve. When used appropriately, they can help support academic promotion and, most importantly, help define and sustain career satisfaction.
Immune checkpoint inhibitors (ICIs) have transformed the treatment of a broad range of malignancies over the past decade. As the scope of indications and the clinical experience expands, oncologists are increasingly confronted with complex scenarios. This chapter addresses three of the most clinically challenging frontiers in ICI use: the safe and effective application of checkpoint blockade in patients with preexisting autoimmune disease, the evolving toxicity landscape of ICI-based combination regimens including chemotherapy + immune checkpoint inhibition, immune checkpoint inhibition + tyrosine kinase inhibitor, and immune checkpoint inhibition + antibody-drug conjugate, and the emerging evidence supporting ICI in solid organ transplant recipients with advanced malignancies.
As systemic therapies for non-small cell lung cancer (NSCLC) have become more effective, interest in their use for improving long-term surgical outcomes has rapidly increased. Imperfect as it is, stage remains the primary means for identifying patients who might benefit from systemic therapy. Recent clinical trials have led to US Food and Drug Administration approval of osimertinib and alectinib as adjuvant treatments for resected pathologic stage II/III EGFR and ALK-mutated NSCLC; their use in the neoadjuvant setting remains subject to trials. Systemic therapy for less common oncogene-addicted NSCLC is also the subject of intense clinical trial activity. An effusion of trials has established the benefit of chemotherapy and immune checkpoint inhibitor therapy combinations in the adjuvant, neoadjuvant, and perioperative settings for patients with clinical or pathologic stage IB to III NSCLC, each of which is now part of the standard of care. Evidence-free consensus expert statements notwithstanding, two very important questions remain to be answered: Which is better-adjuvant or neoadjuvant/perioperative chemoimmunotherapy (and for whom)?; do patients who have pathologic complete response to neoadjuvant immunotherapy benefit from adjuvant immunotherapy? These questions are the subject of two ongoing National Clinical Trials Network trials: CTIU2317-A082304-S2402-Perioperative versus Adjuvant Systemic Therapy in Patients with Resectable NSCLC (PROSPECT-Lung; ClinicalTrials.gov Identifier: NCT04267848)-and S2414-A Randomized Phase III Trial Incorporating Pathologic Response in Participants with Early-Stage NSCLC to Optimize Immunotherapy in the Adjuvant Setting (INSIGHT; ClinicalTrials.gov Identifier: NCT06498635). We discuss why there is sufficient equipoise to justify seeking answers to these two extremely important, patient-centered questions.
Artificial intelligence (AI) is increasingly integrated into oncology across clinical care, research workflows, and translational implementation. This chapter provides a practical overview of these domains, emphasizing opportunities and limitations relevant to real-world oncology practice. In clinical care, AI applications include ambient documentation systems, decision support tools, and remote monitoring platforms. These technologies may reduce administrative burden, assist with evidence synthesis and guideline navigation, and enable longitudinal assessment of symptoms and functional status through wearable and patient-reported data. Emerging tools such as large language models also support patient communication through education, translation, and symptom triage. However, across these applications, performance remains dependent on data quality, validation, and appropriate clinical oversight. In research and scholarship, AI is increasingly used to support grant development, study design, literature review, and manuscript preparation. These tools may improve efficiency, enhance clarity, and assist in identifying research gaps or methodological approaches. At the same time, concerns regarding accuracy, hallucinated content, data privacy, and ethical responsibility require careful oversight. The responsibility for hypothesis generation, methodological rigor, and scientific integrity remains with the investigator. From a translational perspective, a persistent gap exists between model development and clinical deployment. Differences in data quality, infrastructure, and patient populations may limit generalizability, while workflow integration, clinician readiness, and bias mitigation remain critical challenges. Collectively, AI has the potential to enhance oncology care and research, but its impact depends on rigorous validation, equitable implementation, and sustained human oversight.
Bispecific antibodies (BsAb) are a class of T-cell-redirecting therapies used in a variety of advanced malignancies. BsAb can be associated with clinically significant toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections. CRS occurs in up to two thirds of patients and can be associated with ICANS in rare cases. CRS is best treated with tocilizumab, while glucocorticoids are effective in treating both. BsAb-associated CRS and ICANS are mostly low-grade and are confined to the step-up and first full doses. However, the risk of infection persists throughout BsAb therapy and is the leading cause of nonrelapse mortality, particularly with B-cell maturation antigen (BCMA)-targeting BsAbs, due to profound B-cell and plasma cell depletion, resulting in near-universal hypogammaglobulinemia. Infection risk is also increased due to cytopenias, neutropenia and lymphopenia, occurring during the first 6 months of BsAb therapy. Current infection prophylaxis guidelines recommend universal herpes simplex virus, varicella zoster virus, and Pneumocystis jirovecii pneumonia prophylaxis, with primary intravenous immunoglobulin prophylaxis strongly recommended for BCMA-targeting BsAbs. A few other acute toxicities associated with BsAbs include infusion-related reactions generally noted very early (<6 hours) from start of the infusion, and tumor flare reactions usually occurring during the first BsAb cycle. A few important toxicities have been noted with bispecific constructs targeting GPRC5D, including alternation of taste, unintentional weight loss, rash, and nonrash skin and nail toxicities significantly affecting patient's quality of life. A few late but rare complications include progressive multifocal leukoencephalopathy and second primary malignancies, which require continued vigilance. As the use and number of BsAb continues to grow, the knowledge of the characteristics, timing, and management of BsAb toxicities is essential to current clinical practice.
Advances in molecular and genomic techniques have significantly improved our understanding of pediatric brain tumors and enabled the development of targeted therapies directed at specific genetic alterations. The emergence of these therapies is reshaping the management of pediatric brain tumors, offering the potential for more effective and personalized treatment strategies, with reduced toxicity and improved clinical outcomes. This paradigm shift in pediatric neuro-oncology is still at an early stage but is expected to lead to substantial changes in clinical practice in the coming years. Clinical research has already resulted in the approval of several targeted agents, particularly for tumors driven by alterations in the MAP kinase pathway. These successes underscore the importance of integrating molecular diagnostics into routine care. This review summarizes the clinical development and regulatory approval of targeted therapies in pediatric brain tumors. It also addresses key challenges in the design and conduct of clinical trials in this unique population, including small patient numbers. In addition, several critical questions remain unresolved, such as the optimal duration of therapy, the durability of responses, mechanisms of resistance, and the long-term effects of these treatments in children. Finally, this review discusses issues related to access and equity, particularly the availability of these often-costly therapies in low- and middle-income countries, which remains a significant barrier to their global implementation.
This article examines persistent care gaps facing adolescents and young adults (AYAs) with sarcoma, focusing on clinical trial access, germline predisposition, and palliative care. Despite overall progress in oncology, AYAs continue to experience lower clinical trial enrollment-the AYA gap-particularly in rare cancers such as sarcoma, which spans pediatric and medical oncology. The creation of the National Cancer Institute's (NCI) National Clinical Trials Network (NCTN) fostered cross-group collaboration, broadened age eligibility, and streamlined trial activation. Early collaborative sarcoma trials highlighted both the promise and structural challenges of this model, and ongoing reforms aim to improve access, especially in community settings. This article also positions sarcoma as a high-yield context for germline cancer predisposition testing. Contemporary sequencing studies show that 10%-20% or more of patients with sarcoma harbor pathogenic germline variants, often undetected by family history-based criteria. This supports a shift from syndrome-driven to tumor-informed genetic evaluation, particularly for AYAs who frequently fall between pediatric and adult testing frameworks. Finally, the importance of early, age-appropriate palliative care is highlighted. AYAs with sarcoma face substantial symptom burden, functional impairment, prognostic uncertainty, and psychosocial distress. Evidence suggests that integrated palliative care improves quality of life, communication, and potentially survival, yet referrals are often delayed. Together, these topics highlight the need for coordinated, developmentally informed, and biologically integrated approaches to optimize outcomes for AYAs with sarcoma.
Precision oncology has fundamentally reshaped cancer treatment by enabling therapies to be matched to the molecular biology of individual tumors. Advances in next-generation sequencing (NGS) technologies, expanding biomarker discovery, and an increasing number of targeted therapies have made comprehensive molecular testing an integral component of modern oncology practice. Realizing the full clinical impact of these technologies requires understanding not only the biological alterations detected but also the diagnostic workflows through which genomic information is generated and interpreted. NGS-based assays differ substantially in their design, particularly in terms of sequencing breadth, depth, and the chemistry involved in library prep. These technical characteristics influence the types of genomic alterations that can be detected, the analytical sensitivity of testing, and the clinical confidence with which results can be interpreted. Preanalytic variables-including tissue adequacy, nucleic acid quality, and specimen handling-are equally critical, as they determine whether molecular testing can be successfully performed and whether the resulting data accurately reflect tumor biology. Once genomic results are available, clinicians must interpret a diverse range of molecular alterations, including single-nucleotide variants, copy number changes, structural rearrangements, and composite genomic signatures. Structured reporting practices, multidisciplinary interpretation through molecular tumor boards, and evidence-based actionability frameworks help translate these findings into clinically meaningful treatment decisions. Ultimately, maximizing the impact of precision oncology requires coordinated integration across molecular diagnostics, clinical interpretation, and health care delivery systems. By understanding each step of this pathway-from specimen acquisition to therapeutic decision making-clinicians can more effectively translate genomic insights into improved patient outcomes.
Unresectable stage III non-small cell lung cancer (NSCLC) represents a biologically and clinically heterogeneous group of tumors. Concurrent chemoradiotherapy (cCRT) has long been the cornerstone of treatment for patients who are medically inoperable or have unresectable disease because of extensive nodal involvement or local invasion. Despite the curative intent of this approach, only about 30% of patients survive 5 years. Recently, advances have been made in both radiation oncology and medical oncology to incorporate precision medicine techniques and individualize treatment for each patient. Advances in radiation delivery techniques, including intensity-modulated radiotherapy, image-guided radiotherapy, motion management strategies, and adaptive radiotherapy, have improved the precision of treatment to the tumor and lymph nodes while minimizing toxicity to surrounding normal tissues. The introduction of consolidation immunotherapy following CRT has fundamentally changed the treatment paradigm. The phase III PACIFIC trial established consolidation durvalumab as the standard of care, demonstrating significant improvements in progression-free survival (PFS) and overall survival (OS). Similarly, biomarker-driven strategies have begun to reshape management for oncogene-driven tumors. The phase III LAURA trial demonstrated a substantial PFS benefit with consolidation osimertinib in patients with EGFR-mutated stage III NSCLC after definitive CRT. Ongoing research is focused on optimizing treatment sequencing, including induction chemoimmunotherapy approaches, radiation dose intensification strategies such as stereotactic boosts, and integration of targeted therapies for actionable genomic alterations. In this review, we summarize the current evidence guiding the management of unresectable stage III NSCLC, highlight advances in radiation and systemic therapies, and discuss emerging strategies aimed at improving locoregional control and long-term survival.
Lung cancer remains the leading cause of cancer-related mortality worldwide. Although small cell lung cancer (SCLC) accounts for a smaller percentage of lung cancer cases, it has remained a significant contributor to the overall mortality burden because of its inherently aggressive nature. Over several years, and until recently, there have been no major breakthroughs in the management of SCLC. Concurrent chemoradiation with platinum doublet chemotherapy has remained the mainstay of treatment in limited-stage disease, with chemotherapy being the main and only treatment in extensive stage. Despite having an initial good response to those treatments in most patients, progression of cancer has been nearly inevitable, with no additional effective therapeutic options, and the majority of patients with SCLC dying of their disease. Fortunately, the last decade has witnessed some major scientific advances addressing the huge unmet needs in the realm of SCLC management and ushered in renewed hope in the lung cancer community. From approval of immune checkpoint inhibitors and lurbinectedin, a newer chemotherapy agent, to novel immunotherapies such as tarlatamab, a DLL3-CD3 bispecific T-cell engager, and other upcoming promising drugs, the therapeutic armamentarium for SCLC is steadily expanding. In this study, we review the current landscape of both systemic therapy as well as radiation therapy for SCLC, with a focus on major developments over the past decade, current standards of care, and novel therapeutics that are expected to revolutionize the treatment of this aggressive malignancy.
Our global climate is changing-increasing the frequency, intensity, and duration of extreme-weather related disasters-with direct consequences on human health. These extreme weather-related events are not only environmental crises-they are health system crises. Cancer care-from prevention to diagnosis, treatment, survivorship, and end-of-life care-is particularly affected by extreme weather events because of complex, time-sensitive, infrastructure-dependent, multidisciplinary, and resource-intense care. Although these events affect us all, disruptions are particularly impactful on those who live in settings where underlying community and health resources are limited. Therefore, preparedness and resilience planning specific to cancer care is crucial. Existing evidence-informed strategies to prepare and enhance resilience across clinical, institutional, and policy domains include climate resilience integration in clinical training and practice, adaptation of care delivery infrastructure and operations, knowledge and review of local climate vulnerabilities, and strengthened partnerships with community organizations. As extreme weather events increasingly threaten cancer care delivery, proactive, coordinated efforts by oncology professionals, health systems, and policy are essential to ensure high-quality care delivery.
Mortality and morbidity rates remain high in head and neck cancer (HNC). Novel radiopharmaceuticals, injectable therapies, advances in systemic therapy, including novel immunomodulators and cell-based therapies, and system-level changes to address widening global disparities are promising contemporary avenues. Advances are clearly needed to improve outcomes in this disease, but equally important is implementation that maximizes clinical benefit for common and unique subtypes and addresses needs at a global level. HNC remains an active area of investigation where therapeutic innovations are driving new challenges and opportunities.
Artificial intelligence (AI) is reshaping cancer research and clinical oncology by enabling large-scale analysis of complex biomedical data. Although early AI efforts focused on single-modality tasks such as imaging interpretation or pathology classification, contemporary oncology increasingly requires integrated reasoning across heterogeneous inputs, including imaging, digital pathology, and genomics. Multimodal artificial intelligence (MMAI) models represent a major evolution by fusing these data types into unified predictive systems capable of informing diagnosis, risk stratification, treatment selection, and disease monitoring. This manuscript reviews the state of AI in oncology and highlights emerging foundation models within the field. There will be a focus on histopathology, and how this can be incorporated into risk assessment models. There will also be examples of MMAI utility in radiology and spatial proteomics. Additionally, we will discuss ethical and legal implications of MMAI in modern oncology, and recommendations for responsible application within clinical oncology practice.
