Tumor biomarker assessment has traditionally focused on two simple questions: whether a marker is expressed and how strongly it is expressed. This method can still be useful but it is no longer sufficient. The meaning of a marker may vary according to its tissue location, neighboring cell types, and association with a treatment-related microenvironment. As spatial omics technologies progress, cancer research is moving beyond a simple positive-or-negative interpretation of molecular markers. It is therefore important to ask where a marker is positive, which cells are nearby, and whether it is part of an active tissue structure. Spatial proteogenomics brings together protein measurements, transcriptomics, spatial tissue imaging and bioinformatics. This allows for the integration of molecular state, cell state and spatial information. This mini review discusses what this change means for oncology. It focuses on the spatial chain of evidence, the tumor microenvironment, spatial functional units, and the challenge of turning spatial maps into measurements that can be used in the clinic.
As neoadjuvant immunotherapy becomes established as a reference framework in head and neck squamous cell carcinoma management, opportunities emerge to tailor both surgical extent and timing according to treatment response. Spatial regression patterns, in addition to depth of response, should guide extent adaptation, with more conservative surgery considered for patients exhibiting a centripetal regression pattern, provided that intraoperative frozen sections from the pretreatment tumor edges are negative, potentially sparing clinically meaningful structures (e.g., avoiding mandibulectomy in oral cavity cancer). Despite promising preliminary evidence from single-center cohorts, prospective validation of the oncological feasibility and functional benefit of limited resections, supported by protocolized reporting of which structures are spared, remains necessary. Nodal management is more controversial due to frequent discordance between primary tumor and nodal response, as well as the high rate of false-positive post-treatment positron emission tomography (PET) findings. Most neoadjuvant immunotherapy trials have reported no or limited surgical delays; however, the role of response-adapted timing of surgery is under investigation, as early responders may benefit from additional immunotherapy cycles, provided that non-responders can be rapidly expedited to surgery.
Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of cancer globally. Over the last decade, the treatment of the disease has been transformed with the use of immune checkpoint blockade. In the recurrent and metastatic setting, ~50% overall response rates can be achieved, with rapid improvement in patient-reported quality-of-life, and cures confirmed with over five-years follow-up. Neoadjuvant immunotherapy approaches are currently under investigation with the tangible potential of reducing the need for multimodality treatment and facilitating avoidance of the morbidity associated with local therapy. The addition of one year of adjuvant programmed cell death-1 (PD-1) inhibitor therapy following surgery and radiation has improved disease-free survival by 68% in patients with clinicopathologically defined high-risk CSCC, without adverse impact on quality-of-life compared to placebo. This manuscript focuses on reviewing the published literature regarding immunotherapy use for the treatment of CSCC in different clinical settings and explores the data for biological factors that may assist clinicians in selecting patients for an immunotherapy-based treatment approach.
Artificial intelligence (AI) in healthcare holds the promise of more accurate, efficient, and accessible healthcare. In the field of oncology, we experience rapidly evolving possibilities with AI. This paper describes recent insights into the potential benefits of AI at four levels of the health production model: 1. health promotion; 2. early detection and screening; 3. treatment and follow-up; and 4. patient support. The scientific literature points to the (potential) benefits of AI at all of these levels, but also to its pitfalls. It is thereby striking that there is still an important shortage of real-world studies demonstrating the added value of AI, in terms of effectiveness, as well as the way it is embedded in healthcare processes and its impact on human interaction and human–machine interaction. In addition, the evidence regarding the value for money of AI in oncology is very limited. Hence, the potential of AI should be leveraged, and more efforts should be made to systematically allow for assessing its real added value and value for money in the field of oncology.
Introduction: In the United States, immigrant communities of Asian and Pacific Islander (API), African and Caribbean origin are disproportionately burdened by hepatitis B and primary liver cancer (hepatocellular carcinoma). The present study sought to explore the multidimensional factors spanning the top levels of the socioecological model of health (SEM) that influence these communities’ complete engagement in the hepatitis B cascade of care. Materials and methods: Researchers conducted virtual focus groups and key informant interviews with participants from 13 different highly impacted communities across the USA. Qualitative data were analyzed using thematic coding. Results: Findings demonstrate the role and intersection of different SEM constructs in increasing screening, prevention, and management of hepatitis B and hepatocellular carcinoma. The most reported barriers included cost of healthcare services, complex care systems, lack of insurance access, limited health literacy and cultural differences in care utilization. Conclusions: Based on study findings, various recommendations, ranging from systemic health policies to community-led initiatives, are proposed to alleviate the significant health disparities caused by hepatitis B and hepatocellular carcinoma in these communities.
Improved survival after multimodal treatment of primary brain tumors has increased recognition of long-term neurologic sequelae, particularly radiation-induced vascular injury. Cerebral microbleeds (CMBs), visible as hypointense foci on susceptibility-sensitive Magnetic Resonance Imaging (MRI), and radiation-induced cavernomas (RICMs) represent related manifestations of microvascular damage. Their clinical significance and optimal management remain incompletely defined. To present three illustrative cases of radiation-induced cavernomas and CMBs in patients with primary brain tumors and to conduct a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant literature review synthesizing current evidence to inform management. PubMed, Embase, and Web of Science were searched according to PRISMA guidelines. Eligible studies included patients with primary brain tumors treated with radiation therapy that reported outcomes related to radiation-induced vascular injury. CMBs and RICMs share overlapping mechanisms, including aberrant angiogenesis, and common risk factors, with radiation dose and latency most strongly associated with lesion development. CMBs are more frequent, occurring in approximately 50–90% of patients, reflecting diffuse microvascular injury and contributing to gradual cognitive decline. In contrast, cavernomas are less common, occurring in less than 20% of patients in most series, but carry a higher risk of focal neurologic deficits due to intracerebral hemorrhage. Existing evidence is largely retrospective and heterogeneous, limiting firm management recommendations. Risk mitigation centers on radiation dose minimization and precision targeting of lesions. Current data support routine tumor surveillance imaging rather than dedicated screening for microvascular injury, except in cavernomas at elevated hemorrhagic risk, and warrant cautious use of antithrombotic therapy. Prospective adult studies are needed to refine surveillance, anticoagulation management, and interventional thresholds.
Introduction: Immune checkpoint inhibitors (ICIs) significantly improved the survival of patients with advanced malignancies. However, ICIs are associated with immune-related adverse events (irAEs), which can be severe.Case presentation: Here, we present a 69-year-old male patient with metastatic urothelial carcinoma (mUC). In April 2018, he was treated in the KEYNOTE-672/ECHO-307 trial with pembrolizumab (anti-PD1) plus epacadostat (anti-IDO1). After three cycles, he developed encephalitis with involuntary dyskinesias of the face and extremities. These were recognized as faciobrachial dystonic seizures, suggestive of anti-LGI1 encephalitis provoked by the treatment. Serum autoantibodies against LGI1 were detected prior to treatment initiation and increased at the time of encephalitis, confirming the diagnosis. Pembrolizumab and epacadostat were withheld, and symptoms disappeared after administration of high-dose steroids. Still immunocompromised by long-term steroid taper, the patient developed a primo disseminated HSV-1 infection, complicated by hepatitis with acute liver failure. He recovered after intravenous treatment with acyclovir. Seven months thereafter, he had progressive disease of mUC. After careful consideration, pembrolizumab monotherapy was restarted with low-dose steroids and valacyclovir maintenance. The patient completed 24 months of treatment with pembrolizumab without the occurrence of new irAEs and has a durable tumor response for more than four years (last follow-up November 2025).Conclusions: Treatment with ICIs can lead to durable responses in patients with advanced malignancies but can be complicated by severe neurological irAEs. In selected cases, treatment with ICIs can be re-initiated safely and effectively. The neurological phenotype and type of neuronal antibody may aid clinical decision making. Maintenance therapy with low-dose steroids can be considered to minimize the relapse risk of irAEs.
Introduction: Severe and long-lasting lymphopenia occurs in 40% of patients with malignant gliomas and is associated with inferior survival. Inadvertent irradiation of circulating lymphocytes is a major contributor to this lymphopenia. Fingolimod causes striking but reversible lymphopenia by sequestering circulating lymphocytes in lymphoid tissues. Fingolimod could potentially reduce iatrogenic immunosuppression by decreasing the number of lymphocytes in circulation during radiation. However, combining radiation with fingolimod should result in severe lymphopenia. These pilot studies were conducted to determine the safety of this approach in mice and humans.Materials and methods: Ten BALB/c mice received focal brain irradiation (4 Gy × 10 fractions). Half of the mice received intraperitoneal fingolimod (3 mg/kg) before and during the two weeks of radiation. Five patients with newly diagnosed glioblastoma were given fingolimod one week prior to and during the six weeks of concurrent radiation and temozolomide.Results: Mice treated with fingolimod and radiation had more severe lymphopenia than those treated with radiation alone. However, lymphocyte counts and weight loss recovered similarly in both treatment cohorts and no added toxicities were noted. Humans receiving fingolimod developed severe lymphopenia which deepened when radiation and temozolomide were initiated. This was well tolerated and no grade III–IV opportunistic infections were noted.Conclusions: These feasibility studies provide reassuring data on the safety of combining fingolimod with radiation in mice and humans. Further prospective clinical trials are needed to determine if this novel approach to reducing the number of circulating lymphocytes exposed to radiation improves post-radiation lymphocyte counts, responses to immunotherapy, and overall cancer survival.
KRAS (Kristen rat sarcoma viral oncogene homolog) mutations occur in approximately 40–50% of metastatic colorectal cancer (CRC) cases and have long been associated with resistance to anti-epidermal growth factor receptor (EGFR) therapies and poor clinical outcomes. Historically considered “undruggable”, KRAS has recently become a viable therapeutic target following the development of allele-specific inhibitors. The approval of KRAS G12C inhibitors such as sotorasib and adagrasib represents a major milestone, demonstrating clinical activity and improved outcomes compared with standard therapies in the molecularly defined subset. However, single-agent activity remains modest in CRC due to adaptive resistance mechanisms, including compensatory activation of EGFR and downstream signalling pathways. Combination strategies, particularly co-targeting of EGFR and KRAS G12C, have shown enhanced efficacy and are redefining treatment paradigms. Beyond G12C, newer approaches aim to broaden therapeutic coverage through next-generation KRAS inhibitors, pan-RAS or RAS(ON) inhibitors, and allele-specific agents targeting KRAS G12D and KRAS G12V. Additional strategies incorporating Src homology region 2-containing protein tyrosine phosphatase-2 (SHP2), son of sevenless homolog 1 (SOS1), or mitogen-activated protein kinase (MEK) inhibition, as well as emerging immune-based therapies, hold promise in overcoming resistance and improving durability of response. This review summarises recent advances in targeting KRAS-mutant CRC, explores mechanisms of therapeutic resistance, and highlights ongoing efforts to expand precision-based strategies across diverse KRAS alterations.
Locally advanced oral cavity squamous cell carcinoma (OCSCC) presents a significant challenge, with survival rates remaining poor despite advances in surgical technique and chemoradiation. While induction chemotherapy has historically failed to demonstrate a clear survival benefit, the emergence of neoadjuvant immunotherapy and chemoimmunotherapy has opened new avenues for investigation. There is now a rapidly growing focus on the potential for neoadjuvant chemoimmunotherapy to improve survival for locally advanced OCSCC. Moreover, neoadjuvant chemoimmunotherapy holds the potential to reduce preoperative tumor burden, potentially allowing for a response-adapted surgery that optimizes postoperative quality of life while maintaining oncologic safety. Despite these promising early findings, data are heterogeneous and randomized controlled trials are lacking. This narrative review provides an overview and interpretation of current data as it relates to the role of neoadjuvant chemotherapy and immunotherapy to improve survival and postoperative function for locally advanced OCSCC, highlighting the need for standardized protocols and additional trials.
Introduction: Oral cancer is one of the leading malignancies, and its surgical treatment frequently results in complex defects that warrant reconstruction. Although the submental flap (SMF) is a versatile locoregional option, its oncological safety remains debated because of its close proximity to level I lymph nodes.Materials and methods: This retrospective cohort study based on a prospectively maintained database assessed oral cancer patients who had SMF reconstruction between January 2016 and March 2024 and followed untill September 2025. Locoregional recurrence rates were evaluated in this group. Surgical cost was compared between 188 SMFs and 141 free flap reconstructions (FFRs) performed consecutively.Results: A cohort of 2020 cases was included in the study after 139 cases were excluded from the initial pool of 2159 due to inadequate follow-up. The median follow-up was 69 months. 34.6% of cases had pathological nodal involvement (pN+). The likelihood of a locoregional recurrence was 21.7% overall. Compared to node-negative (pN0) patients (19.68%), pN+ patients had significantly higher recurrence rates (25.46%) (p-value = 0.002). Importantly, there was no discernible difference in recurrence between patients with level I metastases and those with metastases at other levels, from a subgroup analysis of pN+ patients (p-value = 0.919). SMF costs considerably less than FFR.Conclusions: The SMF provides acceptable oncological results with recurrence rates comparable to current literature. When used in conjunction with careful lymph node clearance, it does not jeopardize oncological safety, even in patients with level I nodal metastases.
Obesity and diabetes increase cancer risk through insulin resistance, chronic inflammation, and altered growth signaling. Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists reshape this metabolic milieu and are increasingly used for weight loss and glycemic control. Uncertainty persists about whether these agents influence cancer incidence or progression, and there is no consensus on nutrition care during therapy. We present a narrative, mechanism-to-clinic review that synthesizes randomized and observational human studies alongside translational evidence on insulin/IGF-1 pathways, adipokines, bile acids, and the microbiota. We also integrate practice-focused guidance on preserving lean mass, monitoring micronutrients, and managing gastrointestinal tolerance while on these agents. Current human evidence does not show a consistent increase in overall cancer risk with these therapies; however, signals are heterogeneous across tumor sites and follow-up remains limited. Randomized trials rarely adjudicate cancer outcomes, and pharmacovigilance and preclinical results are mixed and context-dependent. Weight loss and improved insulin sensitivity plausibly reduce pro-tumorigenic signaling, whereas rapid weight reduction may threaten muscle mass unless accompanied by proactive nutrition support and resistance exercise. Available data suggest no uniform carcinogenic signal from GLP-1/GIP therapies to date, but organ-specific effects and long-term safety require rigorous, adequately powered follow-up. Dietitians and oncology teams should co-manage patients using high-quality protein distributed across meals, fiber-rich, low-glycemic dietary patterns (such as Mediterranean-style eating), resistance exercise, and targeted micronutrient monitoring, alongside standardized recording of cancer-relevant outcomes.
Introduction: For women with breast cancer, contraception is a challenge in the management of their sexual and reproductive health, and sexual health problems are overlooked despite being commonly experienced side effects of anti-cancer therapies. The objective was to describe trends in contraceptive counselling and sexual health problem management at a tertiary metropolitan comprehensive cancer centre.Materials and methods: A descriptive retrospective audit of the Electronic Medical Records (EMR) of women aged 18–50 with early-stage breast cancer was conducted. Data were entered into REDCap, and descriptive statistics and confidence intervals for proportions were calculated. Fisher’s Exact Testing was used.Results: Ninety-four records were analysed. Under half (49% [46/94], 95% CI: 38–59%) had a contraceptive method documented (including no contraception; n = 18), and 11% (10/94, 95% CI: 5–19%) had contraceptive counselling. Whilst patients taking tamoxifen had a greater frequency of counselling than patients on other oral therapies, the likelihood was not significant (p = 0.108). Eighteen patients were on hormonal contraception during their initial consultation; however, only nine patients had clinicians document a change. The majority (76%, 95% CI: 66–84%; n = 71) had a sexual and reproductive history taken, and twenty-three reported sexual health issues. The most common side effects of anti-cancer therapies were body image, emotional symptoms, and libido.Conclusions: Contraceptive counselling and sexual health are poorly documented in breast cancer patients’ overall treatment, suggesting they are either under-prioritised and/or challenging to record. Contraceptive prescribing for women with hormonally mediated cancers is also not in accordance with clinical guidelines, increasing women’s pregnancy risk.
Introduction: Testicular cancer is one of the most curable malignancies; however, a growing number of men live with the physical and mental health sequelae of the disease and its related treatments. Although supportive care research and programs for this population have expanded, engagement remains low. Sport has been identified as a potential gender-sensitized, community-based platform for delivering supportive care. The purpose of this study was to explore the perspectives of key clinical and community sport personnel perspectives on the feasibility, acceptability, and implementation considerations of a sport-based supportive care intervention for men living with and beyond testicular cancer.Materials and methods: Thirteen semi-structured interviews were conducted with testicular cancer care clinicians (n = 7) and community sport personnel (n = 6). Data were analyzed using an inductive, reflexive thematic analysis to identify key patterns and themes related to supportive care delivery through sport.Results: Three central themes were generated: (i) disrupted trajectories and unmet supportive care needs, (ii) the locker room method, and (iii) knowing when to pass the ball. These themes highlight the complex supportive care needs of young men with testicular cancer, the perceived value of informal peer-based sport environments for fostering engagement, and the importance of clearly defined roles and collaboration between clinical and community sectors.Conclusions: Sport-based supportive care interventions may represent a feasible and acceptable approach for men living with and beyond testicular cancer. Future interventional research should continue to meaningfully involve both clinical and community partners to enhance the relevance, accessibility, and sustainability of supportive care initiatives for this population.
Thoracic malignancies, driven primarily by lung cancer, are the leading cause of cancer-related death worldwide. Artificial intelligence (AI) has shown considerable potential in thoracic oncology, particularly in medical imaging-based applications that improve diagnosis and prognosis. Although many studies have explored diverse AI models across various imaging modalities, most studies remain retrospective, with few prospective or qualitative assessments involving end-users. To assess the current landscape of translational imaging-based AI research in thoracic malignancies, we conducted a scoping review of post-diagnostic models to predict treatment response, patient survival, and precise tumor staging and identified 19 eligible studies that demonstrated potential clinical applicability with external validation. This review summarizes recent advances, as well as major challenges related to data management, model evaluation, and generalizability across clinical settings. Based on these findings, we propose recommendations for robust validation frameworks, standardized reporting of methods for replication, and responsible integration of AI tools into the clinic. Adoption of these recommendations may help bridge the gap between promising models and clinical integration, leading to a meaningful impact on patient care.
Circulating tumour DNA (ctDNA), often referred to as liquid biopsy, is a promising, minimally invasive biomarker in both early-stage and metastatic colorectal cancer (CRC). In early-stage CRC, ctDNA allows the detection of minimal residual disease (MRD) after curative-intent surgery, enabling the identification of patients at higher risk of recurrence and potentially guiding adjuvant therapy decisions. Serial analysis of ctDNA can be performed to assess the efficacy of adjuvant chemotherapy by providing an early molecular read-out of treatment response, and during surveillance to detect molecular recurrence prior to radiological or clinical relapse. In the advanced setting, ctDNA holds promise as a minimally invasive method of detecting emerging resistance mutations and monitoring response to therapy over time. This review highlights the current landscape of evidence, the evolving clinical applications and limitations of ctDNA in colorectal cancer.
Biliary tract cancers are a rare and lethal group of malignancies arising from the gallbladder or intra- or extrahepatic bile ducts. Despite advances in management, prognosis for unresectable disease remains dismal. In recent years, chemoimmunotherapy has superseded chemotherapy alone in first-line treatment of advanced biliary tract cancer with modest improvements in overall survival. The high frequency of somatic mutations, particularly in intrahepatic cholangiocarcinoma, has opened the door to an increasing number of matched targeted therapies, with fibroblast growth factor receptor (FGFR), isocitrate dehydrogenase 1 (IDH1), and human epidermal growth factor receptor 2 (HER2)-directed therapies now approved for second-line treatment of advanced biliary tract cancers, and RET, BRAF, and neurotrophic receptor tyrosine kinase (NTRK)-directed treatments available via tumour-agnostic approvals. Key to ongoing progress, including the probable shift in matched targeted therapies into the first-line setting, will be the uptake of upfront and broad molecular testing to maximise therapeutic options, identify and recruit suitable patients to large clinical trials, and ultimately improve patient outcomes. Here, we discuss in detail current and emerging systemic therapies for biliary tract cancers and future directions.
Phase 1 clinical trials are a critical step in oncology drug development. Historically, these first-in-human trials focused on dose–toxicity profiling in heterogeneous populations. With the emergence of novel anticancer therapies, trial design has shifted toward model-based and adaptive dose-escalation designs, improving dose optimization, and now incorporates biomarker-driven patient selection and multiple objectives, including early efficacy assessment, which accelerates drug development. Hence, phase 1 clinical trials have undergone substantial transformation over recent decades, with a marked impact on response rates and phase 1 units that conduct these trials. By transforming early-stage drug discovery and target identification as well as predicting drug efficacy and toxicity, the implementation of artificial intelligence into early-phase cancer research will further accelerate the discovery of novel anticancer drugs and significantly transform today’s phase 1 trials, ultimately resulting in an increase in phase 1 clinical trials in the near future. In this narrative review, we address the importance of clinical phase 1 trials for oncology drug development, highlight their continuous evolution over the past decades to date, and discuss how this affects phase 1 units and their investigators, as well as exploring the impact of artificial intelligence on phase 1 trials in the coming years.
Background: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) remains the standard of care for early-stage breast cancer (ESBC), supported by decades of randomized trials demonstrating reduced local recurrence and improved survival. Recent advances in radiobiology, molecular profiling, and treatment delivery have expanded the range of RT options, allowing for more personalized, risk-adapted approaches. Objective: This review aims to summarize and critically evaluate current radiotherapy strategies for ESBC, with a focus on hypofractionated regimens, radiotherapy omission, and the influence of patient age on treatment selection and outcomes. Content: We discuss the clinical evidence supporting moderate and ultra-hypofractionated RT schedules, including long-term results from the START and FAST-Forward trials, and highlight the gradual adoption of these regimens into practice. We examine barriers to widespread implementation, such as concerns about long-term toxicity in younger patients and financial disincentives in certain healthcare systems. The review also explores RT omission in low-risk elderly patients, emphasizing ongoing debates surrounding adherence to endocrine therapy, patient quality of life, and evolving trial data. Age-specific considerations, including differences in tumor biology, life expectancy, and treatment tolerance, are integrated throughout the discussion to underscore the need for individualized treatment planning. In this context, it is important to consider the side effects of hormonal therapy, as younger women may experience greater impacts on fertility, sexual health, and daily functioning, while older women are more prone to bone loss, joint pain, and metabolic effects, all of which influence quality of life and adherence to treatment. Conclusions: As evidence continues to support shorter and more targeted RT regimens, clinical practice must adapt to balance efficacy, safety, and patient-centered outcomes. Treatment decisions should increasingly reflect patient-specific factors rather than age alone. Ongoing trials and extended follow-up will further refine these approaches, advancing the paradigm of personalized radiotherapy in early breast cancer.
Introduction: The role of elective neck dissection (END) in clinically node-negative patients undergoing primary or salvage total laryngectomy (STL) remains controversial. The aim of this study was to evaluate nodal stage migration and the rate of occult nodal metastases in patients undergoing primary versus salvage laryngo(pharyng)ectomy.Materials and Methods: In this retrospective single-center study, patients treated between 2010 and 2020 at a tertiary university hospital were included. All patients underwent preoperative ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) as well as contrast-enhanced CT or MRI for staging. Clinical nodal status (cN) was compared with final pathological nodal classification (pN) to assess nodal stage migration and occult metastases (cN0 to pN+). Outcomes were analyzed descriptively and comparatively between primary and salvage surgery groups.Results: A total of 70 patients were included (32 primary surgery, 38 salvage surgery). Nodal upstaging occurred more frequently in the primary surgery group (38%) compared with the salvage group (18%). In the salvage cohort, 4 of 31 clinically node-negative patients (12.9%) were found to have occult nodal metastases. No nodal downstaging was observed in the salvage group.Conclusions: Nodal stage migration occurs in both primary and salvage laryngo(pharyng)ectomy. The observed rates of occult nodal disease, particularly in the salvage setting, support careful patient selection regarding END while balancing oncologic risk and procedure-related morbidity
