The management of node-positive prostate cancer (N1 PCa) remains a subject of ongoing debate, with growing evidence supporting the role of radiation therapy (RT) alongside systemic therapy. Traditionally, N1 disease was...The management of node-positive prostate cancer (N1 PCa) remains a subject of ongoing debate, with growing evidence supporting the role of radiation therapy (RT) alongside systemic therapy. Traditionally, N1 disease was considered metastatic; however, advancements in imaging and treatment have redefined its clinical relevance. This narrative review evaluates current evidence, focusing on recent literature and ongoing clinical trials in N1 PCa, both in the definitive and postoperative setting. Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) has significantly improved staging accuracy, leading to stage migration and increased consideration of RT for patients with cN1 disease. Both retrospective and prospective studies suggest that RT combined with androgen deprivation therapy (ADT) improves survival compared to ADT alone. Robust data from large clinical trials and ongoing studies support the use of whole-pelvic RT (WPRT) with dose escalation to involved nodes. The optimal management of postoperative pN1 disease remains controversial, with strategies ranging from observation to early salvage or adjuvant RT, often combined with systemic therapy. The ideal RT volume, dose, and systemic therapy combinations continue to be investigated. However, several ongoing trials are paving the way for more refined and effective treatment approaches. This review highlights key trials that may significantly improve the management of N1 PCa in the near future.
Prostate cancer represents the most common nonskin malignancy among males in the United States. There are a variety of treatment options for men with localized prostate cancer including surgery or radiation therapy. Whil...Prostate cancer represents the most common nonskin malignancy among males in the United States. There are a variety of treatment options for men with localized prostate cancer including surgery or radiation therapy. While recent advances in prostate cancer screening and treatment have improved prostate cancer outcomes, toxicity mitigation and attention to patient-related quality of life is critical. The employment of particle therapy may help us accomplish these objectives by allowing for increased dose escalation to tumor while lowering integral dose and improving dose distribution to organs at risk. Herein, we explore the use of particle bream radiotherapy for the treatment of prostate cancer and its evidence to date. More prospective data is needed on whether these therapies translate into clinically meaningful improvements in prostate cancer care, both from a quality of life and outcome perspective.
Radiotherapy remains a cornerstone in the management of prostate cancer (PCa) with continuous technological advancements significantly improving precision and reducing treatment-related toxicity. Among these innovations,...Radiotherapy remains a cornerstone in the management of prostate cancer (PCa) with continuous technological advancements significantly improving precision and reducing treatment-related toxicity. Among these innovations, adaptive radiotherapy (ART) is revolutionizing the field by enhancing treatment precision through advanced imaging, real-time motion tracking, and on-table adaptive planning. ART carries the potential to optimize therapeutic outcomes by adjusting radiation dose in response to anatomical changes that previously could not be accounted for, thus minimizing damage to healthy tissue and increasing the delivery of dose to therapeutic targets. Magnetic resonance (MR) and computed tomography (CT) imaging have played pivotal roles in ART by providing detailed anatomical and functional insights for treatment planning and realtime guidance. This review explores the technical principles, clinical applications, and recent technological developments of ART in the management of PCa. It describes both offline and online ART workflows and compares CT-guided and MR-guided approaches, outlining how each modality enhances the precision of radiation delivery through improved visualization, auto-segmentation, and plan adaptation capabilities. As ART technologies continue to evolve, these imaging-guided modalities are poised to refine prostate RT by enabling safer dose escalation, minimized toxicity, and ultimately, improved patient outcomes.
Prostate cancer is the most commonly diagnosed cancer in men worldwide. Radiotherapy is an integral component for the treatment of localized prostate cancer. Radiobiologically, prostate cancer is sensitive to an increase...Prostate cancer is the most commonly diagnosed cancer in men worldwide. Radiotherapy is an integral component for the treatment of localized prostate cancer. Radiobiologically, prostate cancer is sensitive to an increased dose of radiotherapy delivered per fraction, called "hypofractionation", due to intrinsic differences in the rate of cancer cell growth and repair of DNA damage. Hypofractionation delivers planned treatment over fewer radiotherapy sessions compared to conventional fractionation and has been shown to be noninferior to conventional fractionation with an acceptable toxicity profile. Ultra-hypofractionation, often delivered via stereotactic body radiotherapy (SBRT), further reduces the number of treatments by using even larger doses per fraction and has shown promising results with high biochemical control rates and low rates of late toxicity. The adoption of hypofractionated and ultra-hypofractionated schedules improves resource utilization in radiation oncology without compromising patient safety or efficacy. Ongoing research continues to refine patient selection, fractionation schemes, and incorporates advanced imaging, precise treatment planning, and motion management techniques to help mitigate toxicity and optimize outcomes in localized intermediate and high-risk disease.
Risk stratification is a cornerstone of the clinical management of nonmetastatic prostate cancer. Conventional risk stratification has relied on clinical and pathologic variables, which allow for patients to be placed in...Risk stratification is a cornerstone of the clinical management of nonmetastatic prostate cancer. Conventional risk stratification has relied on clinical and pathologic variables, which allow for patients to be placed into risk groups that help guide prognostication and treatment recommendations. However, the performance of conventional risk stratification systems is suboptimal, leading to undertreatment for some patients and overtreatment (with potentially avoidable side-effects) for others. In recent years, a number of novel biomarkers, with potential to significantly advance risk stratification, have appeared, including molecular, imaging, and digital pathology biomarkers. This review summarizes the technologies behind these novel biomarkers, their established clinical roles, challenges and limitations, and future directions.
Prostate-specific membrane antigen/positron emission tomography (PSMA-PET) changed the diagnostic approach in prostate cancer (PCa), providing superior diagnostic accuracy compared to conventional imaging (CI) modalities...Prostate-specific membrane antigen/positron emission tomography (PSMA-PET) changed the diagnostic approach in prostate cancer (PCa), providing superior diagnostic accuracy compared to conventional imaging (CI) modalities like computed tomography (CT), bone scintigraphy (BS) or other PET radiopharmaceuticals like choline or fluciclovine. This improved diagnostic accuracy plays a crucial role in its synergy with radiotherapy, particularly in the context of metastasis-directed therapy. Even in advanced stages of prostate cancer, the synergy with radiotherapy is evident in the promising results emerging from the combination of RT and RLT. To evaluate the value of PSMA as biomarker, the technological advancements in PSMA-PET, and its integration into clinical practice, focusing on its impact on RT and RLT. A comprehensive nonsystematic literature review was performed using PubMed/MEDLINE and EMBASE biomedical databases. Literature search was updated until March 2025. The most relevant studies have been summarized, giving priority to registered clinical trials and multicenter collaborations. The higher accuracy of PSMA-PET is advancing RT planning in PCa, from initial staging to salvage and metastasis-directed therapy. Ongoing trials combining RLT with external beam radiotherapy (EBRT) may expand its role into earlier stages. Key challenges include the need for long-term outcome data, standardization, cost-effectiveness, and avoiding overtreatment. Future efforts should optimize PSMA-guided RT, evaluate novel RLT combinations, and identify predictive biomarkers for personalized care. The synergy between PSMA-PET and radiotherapy enables a more effective therapeutic approach across both early and advanced stages of PCa, particularly through the promising integration with RLT.
Prostate cancer remains one of the most commonly diagnosed malignancies worldwide, yet significant disparities and inequities persist across the continuum of care. Black men face a disproportionate burden, exhibiting the...Prostate cancer remains one of the most commonly diagnosed malignancies worldwide, yet significant disparities and inequities persist across the continuum of care. Black men face a disproportionate burden, exhibiting the highest incidence and mortality rates. Older patients often receive less aggressive treatment despite higher risk profiles. Insurance status critically influences timely diagnosis and treatment; uninsured and underinsured individuals are more likely to experience delays in care, leading to worse prognoses. Rural residents and those with lower-income have limited access to specialized care while those of lower education status have reduced screening and later-stage diagnoses. Disparities extend to biopsy techniques and treatment decisions. Black and other underserved populations are less likely to undergo targeted biopsies, which have been shown to improve tumor characterization and risk stratification. Additionally, they are more likely to receive non-definitive management, even when presenting with high-risk, potentially lethal disease. Socioeconomic barriers, healthcare access, provider biases, and underrepresentation and exclusion from clinical trials further exacerbate these disparities, limiting opportunities for precision medicine approaches tailored to diverse populations. Addressing these inequities requires a multifaceted approach, including increasing access to advanced diagnostics and therapeutics, improving representation in research, and integrating social determinants of health into prostate cancer management strategies. Emerging evidence on radiogenomics and molecular biomarkers offers promising avenues for personalized care, but equitable implementation is crucial to avoid widening existing gaps. A concerted effort to eliminate disparities is essential to achieving equitable prostate cancer outcomes across all populations.
Long-term care for head and neck cancer (HNC) survivors is complex. Despite an improvement in survival and the evolution of treatment paradigms (de-escalation, targeted therapy), notably in the context of human papilloma...Long-term care for head and neck cancer (HNC) survivors is complex. Despite an improvement in survival and the evolution of treatment paradigms (de-escalation, targeted therapy), notably in the context of human papillomavirus (HPV)-related oropharyngeal cancers, HNC survivors still experience a wide range of side effects and needs, which impact their functionality, quality of life, survival and require concerted, coordinated survivorship care. In this review, we perform an overview of existing HNC survivorship recommendations within the context of novel evidence, our current understanding of survivorship care, and incorporate them into the Nekhluydov Survivorship Care Framework. This framework provides a novel way to appreciate and comprehensively address all aspects of HNC survivorship care. Further research is crucial to develop evidence-based, patient-centered personalized approaches to survivorship care in different HNC populations and understand barriers to successful implementation.
Semin Radiat Oncol
· 2025 Apr · PMID 40090753
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Radiation-induced xerostomia (RIX) is a common and debilitating side effect of head and neck cancer radiotherapy, significantly impacting patients' quality of life. This review comprehensively summarizes the current unde...Radiation-induced xerostomia (RIX) is a common and debilitating side effect of head and neck cancer radiotherapy, significantly impacting patients' quality of life. This review comprehensively summarizes the current understanding of RIX, encompassing its clinical quantification, underlying pathophysiology, and established and emerging treatment modalities. We explore various objective and subjective measures used to quantify salivary flow and assess the severity of xerostomia in clinical settings. The pathophysiological mechanisms leading to RIX are elucidated, including radiation damage to salivary glands, alterations in saliva composition, and the role of inflammatory processes. Current treatment strategies, such as saliva substitutes and stimulants, are discussed alongside their limitations. Furthermore, we delve into novel investigational approaches, including gene therapy, stem cell transplantation, and pharmacologic interventions, offering promising avenues for future RIX management. This review provides clinicians and researchers with a comprehensive overview of RIX, highlighting the need for continued research to develop more effective preventative and therapeutic strategies to alleviate this burdensome condition.
Oral mucositis (OM) is a common side effect of radiation therapy for head and neck cancer (HNC). Despite the medical advances in cancer therapy, OM is still virtually inevitable in patients being irradiated for neoplasms...Oral mucositis (OM) is a common side effect of radiation therapy for head and neck cancer (HNC). Despite the medical advances in cancer therapy, OM is still virtually inevitable in patients being irradiated for neoplasms of the head and neck. The initial signs of oral mucositis typically manifest after cumulative doses between 15 and 20 Gy, with ulceration formation by 30 Gy and reaching peak severity in the week after radiation treatment completion (generally 60-72 Gy in management of HNC), then resolving over the 3-4 weeks following treatment completion. Severe oral mucositis (SOM), defined as WHO grade 3 and grade 4, occurs in 65-70% of patients receiving concurrent cisplatin and radiation therapy for locoregionally advanced HNC. WHO grade 3 or 4 oral mucositis leads to risk of systemic infection, severe pain, reduced oral intake which can lead to dehydration, significant weight loss and malnutrition, need for feeding tube placement and hospitalization. The clinical and economic impact, not to mention the impact on patient quality of life from oral mucositis has been well studied. As mucositis is commonly the dose-limiting factor leading to disruption or delay in cancer therapy, establishment of evidence-based guidelines has been paramount in supportive care management of these patients. Improvements in the prevention and treatment of oral mucositis remain essential to better patient outcomes. Here we review the current standard of care, recent successes and failures in development of therapies to mitigate OM, share patient and provider educational resources, and describe on-going and future directions of research in this area.
Head and neck cancer is estimated to result in 71,000 new cancer diagnoses and 16,000 deaths in 2024. Of these cases, approximately 14% will be metastatic. Recent changes in treatment paradigms have established immunothe...Head and neck cancer is estimated to result in 71,000 new cancer diagnoses and 16,000 deaths in 2024. Of these cases, approximately 14% will be metastatic. Recent changes in treatment paradigms have established immunotherapy as a cornerstone of treatment in the metastatic and recurrent setting. While immunotherapy has undoubtedly improved outcomes and can lead to long term durable responses in select patients, overall response rates remain suboptimal, with approximately 13%-20% of patients responding to immunotherapy in most studies. This review aims to provide an overview of the current treatment landscape of immunotherapies in head and neck malignancies. Additionally, we aim to discuss the future of immunotherapy, as well as novel targets and therapeutic platforms that may continue to change the treatment paradigm in this disease.
Reirradiation of the head and neck presents one of the most complex and challenging scenarios faced by (for) clinicians due to the narrow therapeutic window. Its use is increasing in clinical practice, often guided by em...Reirradiation of the head and neck presents one of the most complex and challenging scenarios faced by (for) clinicians due to the narrow therapeutic window. Its use is increasing in clinical practice, often guided by empirical and pragmatic approaches due to the limited availability of high-level evidence from randomized clinical trials. Successful reirradiation requires a precise balance between tumor control probability (TCP) and normal tissue complication probability (NTCP). Advances in radiation technologies, including intensity-modulated radiation therapy (IMRT), proton beam therapy (PBT), and stereotactic body radiation therapy (SBRT), have enabled more precise high-dose delivery, potentially improving dose distribution and reducing severe toxicity. This review explores current state-of-the-art approaches to reirradiating recurrent head and neck cancer, focusing on modern reirradiation techniques and critically assessing the literature on their clinical application, integration with systemic therapy, and future directions. It also addresses key practical challenges related to patient selection and toxicity/risk management, offering a comprehensive overview of the evolving treatment landscape and highlighting some of the most complex issues clinicians face in reirradiation.
Radiation resistance in head and neck squamous cell carcinoma (HNSCC), driven by intrinsic and extrinsic factors, poses a significant challenge in radiation oncology. The key contributors are tumor hypoxia, cancer stem c...Radiation resistance in head and neck squamous cell carcinoma (HNSCC), driven by intrinsic and extrinsic factors, poses a significant challenge in radiation oncology. The key contributors are tumor hypoxia, cancer stem cells, cell cycle checkpoint activation, and DNA repair processes (homologous recombination and non-homologous end-joining). Genetic modifications such as TP53 mutations, KRAS mutations, EGFR overexpression, and abnormalities in DNA repair proteins like BRCA1/2 additionally affect radiation sensitivity. Novel radiosensitizers targeting these pathways demonstrate the potential to overcome resistance. Hypoxia-activated drugs and gold nanoparticles enhance the efficacy of radiotherapy and facilitate targeted distribution. Integrating immunotherapy, especially immune checkpoint inhibitors, with radiation therapy, enhances anti-tumor responses and reduces resistance. Epigenetic alterations, such as DNA methylation and histone acetylation, significantly influence radiation response, with the potential for sensitization through histone deacetylase inhibitors and non-coding RNA regulators. Metabolic changes linked to glucose, lipid, and glutamine metabolism influence radiosensitivity, uncovering new targets for radiosensitization. Human papillomavirus (HPV)-associated malignancies exhibit increased radiosensitivity relative to other tumors due to impaired DNA repair mechanisms and heightened immunogenicity. Furthermore, understanding the interplay between HPV oncoproteins and p53 functionality can enhance treatment strategies for HPV-related cancers. Using DNA damage response inhibitors (PARP, ATM/ATR), cell cycle checkpoint inhibitors (WEE1, CHK1/2), and hypoxia-targeted agents as radiosensitizing strategies exhibit considerable promise. Immunomodulatory approaches, including PD-1 and CTLA-4 inhibitors in conjunction with radiation, enhance anti-tumor immunity. Future directions emphasize personalized radiation therapy using genetics, sophisticated medication delivery systems, adaptive radiotherapy, and real-time monitoring. These integrated strategies seek to diminish radiation resistance and improve therapeutic efficacy in HNSCC.
Head and neck squamous cell carcinoma of unknown primary (SSCUP) presents a clinically challenge disease process requiring elaborate multidisciplinary collaboration for effective treatment. With the rise in prevalence HP...Head and neck squamous cell carcinoma of unknown primary (SSCUP) presents a clinically challenge disease process requiring elaborate multidisciplinary collaboration for effective treatment. With the rise in prevalence HPV associated squamous cell carcinoma, it has become the predominant etiology SCCUP of the head and neck. Advances in the diagnostic evaluation and treatment of SCCUP have led to higher detection rates of primary lesions, improved disease-free and overall survival outcomes, and reduced morbidity for patients. Furthermore, delineation of the molecular implications of HPV positivity and disease behavior has opened avenues for successful de-escalation of treatment. Transoral robotic surgery (TORS), as well as dose reduction protocols show significant promise for oncologic efficacy with minimization of treatment related morbidity.
The dominant treatment paradigm for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) involves postoperative or definitive radiotherapy with concurrent cisplatin chemotherapy. Despite years of researc...The dominant treatment paradigm for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) involves postoperative or definitive radiotherapy with concurrent cisplatin chemotherapy. Despite years of research investigating de-intensified treatment, cisplatin-based chemoradiotherapy remains the standard, yet it is associated with significant acute and chronic toxicity. However, due to shared risk factors, such as advanced age, and tobacco and alcohol use, patients with HNSCC frequently have comorbid illnesses that impact treatment tolerability, adding complexity to treatment-related decision-making. In addition, many patients have medical contraindications to cisplatin, requiring alternative treatment strategies. It is thus important to consider how well patients are likely to tolerate treatment, and how to adapt treatment in response to a patient's condition, when weighing treatment options. In this review, we aim to offer readers guidance in managing the elderly or comorbid patient with HNSCC, with particular attention to (i) approaching comorbidity and fragility assessment to make determinations on intensity of treatment, (ii) considering primary treatment modality (eg, surgery vs radiotherapy, chemo-radiotherapy vs radiotherapy alone) and (iii) choice of concurrent systemic therapy agent.
The use of hypofractionated radiation therapy has increased among many cancers, although its use in head and neck cancers remains limited due to concerns regarding acute and late toxicities. Recent retrospective and pros...The use of hypofractionated radiation therapy has increased among many cancers, although its use in head and neck cancers remains limited due to concerns regarding acute and late toxicities. Recent retrospective and prospective studies demonstrate the preliminary safety and efficacy of hypofractionation in the definitive, postoperative, and preoperative settings for head and neck treatment. This article seeks to comprehensively review the rationale and data for novel fractionation schemes in this disease site. We also provide practical clinical and dosimetric insights based on our institutional experiences with hypofractionation in head and neck cancers.
Nasopharyngeal carcinoma (NPC) is sensitive to chemotherapy and radiotherapy, with current treatment recommendations largely based on TNM-stage. Radiotherapy remains the backbone of treatment for NPC. Over the past decad...Nasopharyngeal carcinoma (NPC) is sensitive to chemotherapy and radiotherapy, with current treatment recommendations largely based on TNM-stage. Radiotherapy remains the backbone of treatment for NPC. Over the past decades, the addition of concurrent chemotherapy to radiotherapy for early-stage disease, and the combination of induction chemotherapy (IC) or adjuvant chemotherapy (AC) with chemoradiotherapy vs chemoradiotherapy alone for advanced disease have led to substantial improvements in survival of patients with NPC. Nonetheless, in the era of precision oncology, there is growing recognition that patients with NPC are clinically heterogeneous even within the same stage-group, and future advances must focus on individualisation of systemic therapy and radiotherapy. In this review, we summarised the published evidence on EBV DNA as a biomarker for clinical stratification and treatment response in NPC, and discussed some of the ongoing clinical trials of EBV DNA-directed personalisation of systemic therapy in locoregionally-advanced disease. Next, we assessed the evidence concerning individualised radiotherapy strategies for target volume delineation of the primary tumour and cervical nodes that ought to be based on individual tumour extent and IC response (for locoregionally-advanced NPC) as opposed to the historical one-size fits all approach. In the same vein, radiotherapy dose de-escalation may be considered in good responders to IC, whereas for the poor responders, altered fractionation or dose escalation may be required to target resistant disease. These concepts are particularly relevant in the era of combinatorial immune checkpoint blockade therapy with radiotherapy, where preservation of circulating immune cells is crucial to evoke immune-mediated antitumour cytotoxicity.
Human papillomavirus (HPV) associated oropharyngeal carcinoma is currently the most frequently diagnosed head and neck cancer in the United States. Due to the generally high cure rates with standard therapies, de-intensi...Human papillomavirus (HPV) associated oropharyngeal carcinoma is currently the most frequently diagnosed head and neck cancer in the United States. Due to the generally high cure rates with standard therapies, de-intensification strategies are being explored to reduce acute and long-term side effects. For patients treated with definitive chemoradiation, unselected de-escalation has shown worse progression-free survival compared to standard therapy. Concurrently, surgical management is becoming more prevalent, and adjuvant de-escalation appears promising. Further research is required to identify optimal candidacy for adjuvant de-escalation and to understand the relationship between dose and volume de-escalation. Biomarkers such as ctDNA may assist in candidate selection, but validation and alignment with pathological criteria are necessary.