This study aimed to examine utilization, testing sequences, and associated genomic testing costs of companion diagnostics (CDx) and comprehensive genomic profiling (CGP) among Japanese patients with nine representative solid tumors. This retrospective study used anonymized data, from Medical Data Vision Co., Ltd. (MDV; January 2015-March 2025) and JMDC Inc. (JMDC; January 2015-January 2025), for patients with solid tumors of nine cancer types who underwent CDx and/or CGP testing or received any cancer treatment. Patient demographics, distribution and testing sequences of CDx and CGP, and associated genomic testing costs per patient were evaluated. Proportions of CDx and CGP testing varied across nine cancer types. Most patients underwent CDx testing once or twice, although some cohorts, particularly with non-small cell lung cancer (NSCLC), were tested thrice or more. Biliary tract cancer demonstrated the highest proportions for CGP testing alone, and both CDx and CGP testing. For both CDx and CGP testing, the greatest median costs were observed for ovarian and breast cancers, with bimodal peaks near US dollars (USD) 4000 and USD 5000. Median CDx costs were equal to or higher for patients who underwent both CDx and CGP testing compared with those who had CDx testing alone, particularly in breast, pancreatic, prostate, and ovarian cancers. For CDx testing alone, NSCLC, ovarian cancer, and prostate cancer had the highest costs, with a small peak near USD 1333. These results were mostly consistent across databases. Multiple CDx testing followed by CGP testing increased genomic testing costs per patient. Early implementation of CGP testing could reduce redundant testing and associated delays in treatment, thereby contributing to lower overall healthcare costs and more efficient treatment selection amid rapid advances in targeted therapies.
Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) has major physical and psychosocial burdens. Although treatment challenges are well recognized, few studies have explored the full LA-HNSCC experience from first symptoms through to post-treatment recovery and survivorship. This exploratory, qualitative study sought to understand patient and caregiver perspectives across the LA-HNSCC journey. US adults with lived experience of LA-HNSCC (seven patients; two caregivers) participated in Johnson Johnson’s Head Neck Cancer Patient Engagement Research Council via virtual focus groups and online bulletin board activities. Transcripts and written responses were thematically analyzed using an a priori framework of three key stages: diagnosis and treatment planning, treatment, and post-treatment recovery and survivorship. Diagnostic journeys varied, with delays to diagnosis commonly perceived by participants as being attributed to multiple factors, including misinterpreted symptoms, difficulty accessing specialists, and limited provider awareness. Participants reported fear, uncertainty, and information overload during early decision-making. Treatment was described as burdensome, with side effects from radiation and chemotherapy leading to profound functional impairments affecting eating, swallowing, speech, and energy levels. Post-treatment long-term effects such as dry mouth, hearing loss, peripheral neuropathy, and anxiety about recurrence persisted and were often unexpected. Throughout these challenges, participants found strength, encouragement, and hope in peer support networks and valued knowledgeable and empathic communication with providers, as well as access to clear and digestible information; in particular, participants recommended early mental health support, tailored communication, and access to peer mentorship services. These exploratory, qualitative insights highlight unmet informational, psychosocial, and support needs in LA-HNSCC. Patients and their caregivers reported experiencing substantial, long-lasting physical and mental health effects that providers should be aware of to better support and empower patients throughout the care experience. A graphical abstract and patient journey infographic are available for this article. Infographic Head and neck cancer and its treatments can affect important bodily functions such as eating, speaking, and swallowing. The journey of head and neck cancer diagnosis and treatment can be challenging for both patients and their caregivers, including physical side effects and mental health impacts. This study asked a small group of patients with locally advanced head and neck cancer and caregivers to describe their experiences from the first signs of illness through treatment, recovery, and survivorship. Seven patients and two caregivers participated in online focus groups and written activities to share their perspectives. Many participants said they experienced delays before getting a correct diagnosis. Their symptoms were sometimes mistaken for more common issues, and it could be difficult to access specialists. This uncertainty often led to fear and emotional stress. Participants also felt overwhelmed by the amount of information they were given and the tasks and appointments they had to complete before starting treatment. Radiation and chemotherapy treatments led to painful and exhausting side effects that made daily life challenging. After treatment finished, many participants continued to experience unexpected long-lasting effects, including swallowing problems, hearing changes, nerve issues, and anxiety about the cancer returning. Participants found support, encouragement, and hope for the future in talking to other patients, sharing their experiences, and putting energy into healthy lifestyle factors. They valued clear information and access to emotional support. Participants recommended using patient support and mentorship networks, including organizations such as Imerman Angels and the Head and Neck Cancer Alliance.
Androgen receptor pathway inhibitors (ARPIs) are a critical prostate cancer (PC) treatment option. Previous research has suggested that the physical attributes of ARPI medications (e.g., pill formulation, pill shape, pill size, dosing) may influence patients’ treatment satisfaction, adherence, and persistence, which may impact patient outcomes and quality of life. The objective of this study was to describe Mexican clinical experts’ perspectives on how different attributes of pill forms of ARPIs may affect treatment preferences and compliance in patients with PC. This study employed a mixed-methods sequential design. In the first phase, we conducted a targeted literature review (TLR) to frame discussions with clinical experts. In phase 2, we conducted a structured expert elicitation (SEE) comprised of a survey, semi-structured individual interviews, and two focus groups with oncologists and urologists to gather insights about the influence of different ARPI attributes on patient preferences and compliance. In the third phase, we constructed a series of probabilistic mathematical models to analyze the likelihood of patients’ treatment preferences and adherence. The TLR identified pill size, shape, number, frequency, and form as key attributes that influence patients’ experiences and treatment compliance. Simpler regimens and smaller, easier-to-swallow formulations were consistently linked to greater comfort and adherence. In the SEE, participants ranked dosing frequency and pill count as the factors with the greatest influence on patient adherence when efficacy was comparable. During the interviews and focus groups, participants highlighted the importance of ≤ 2 pills/day, once-daily dosing, and small pill size alternatives. Findings from the Monte Carlo models were consistent with the earlier phases, supporting the importance of patient-preferred formulations. Findings from this mixed-methods study indicate that patient-preferred formulations may support better treatment adherence and support consideration of patient preferences in treatment decision-making between clinicians and patients to optimize adherence and outcomes in PC management.
Cancer remains a major public health concern in China, with approximately 2.57 million cancer-related deaths reported in 2022. Real-world studies (RWS), which leverage high-quality real-world data (RWD), can generate robust real-world evidence (RWE) to enhance clinical decision-making and improve patient outcomes across diverse oncology settings. A comprehensive literature search of four bibliographic databases (PubMed, Embase, China National Knowledge Infrastructure, and Wanfang) was conducted to identify oncology-related RWS articles and RWD sources covering Chinese populations from 2015 to 2025. 2606 RWS articles were identified. The findings indicate a growing trend in RWS publications, with a predominant focus on disease epidemiology. A total of 126 databases were extracted. Registries were observed as the main source of RWD. The top three investigated cancer types were digestive system, thoracic, and breast neoplasms. RWD sources are predominantly concentrated in coastal regions, reflecting disparities in the geographical distribution of oncology research. Enhancing data quality and promoting the aggregation of RWD are essential for maximizing the utility of RWD in advancing oncology care in China. Moving forward, standardized regulatory procedures, improved data accessibility, and collaboration across the healthcare ecosystem are essential to unlock the value of RWD and improve patient outcomes. Cancer is a major cause of death in China. Researchers are using real-world data where information is collected from routine health check-ups such as hospitals, registries, and medical records. These types of studies are known as real-world studies. The current comprehensive review investigated published real-world studies on cancer performed in China between 2015 and 2025. Researchers identified four major medical literature databases and observed over 2600 relevant studies involving Chinese patients. From these studies, 126 real-world data sources were extracted and characterized. The number of real-world cancer studies has increased over time. These studies have increasingly focused on disease epidemiology and investigations of therapeutic outcomes. The 126 databases extracted from the studies were predominantly registry and claims. Digestive systems, chest (such as lung cancer), and breast cancer types were the most common databases involving cancer. The coastal region of China has reported that substantial research based on real-world data is unevenly distributed across the country. Improving the quality of real-world data and combining data from different sources could help researchers to better understand cancer in advance cancer care. Data and mutual collaboration among healthcare providers and researchers will be important to completely actualize the benefits of real-world data and improve outcomes for people with cancer in China.
Ciltacabtagene autoleucel (cilta-cel) has demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma (RRMM), supporting the goal of sustained minimal residual disease (MRD) negativity as a marker for potential functional cure, characterized by prolonged treatment-free disease control. Initially, cilta-cel was approved in the US for RRMM after ≥ 4 prior lines of therapy (LOT), and after 1–3 prior LOT in April 2024. This study describes real-world clinical outcomes, including MRD negativity, of cilta-cel after 1–3 prior LOT. Electronic medical records from Loopback Analytics (April 2024–May 2025) were used, supplemented with physician notes. Adults with RRMM treated with cilta-cel after 1–3 prior LOT were included. Post-infusion outcomes (cilta-cel response, MRD negativity, disease progression, and overall survival) were assessed overall and by bridging therapy (BT) regimen. Overall, 120 patients were included (median age 67 years, 43.3
Combinations of an immune checkpoint inhibitor (ICI) + anti-programmed cell death 1 protein (PD-1) or anti-programmed cell death ligand 1 (PD-L1) or an ICI + tyrosine kinase inhibitor (TKI; anti-vascular endothelial growth factor [VEGF]) are the current standard first-line treatments for advanced renal cell carcinoma (RCC). However, novel therapies are needed as treatments for RCC have relied on the same mechanisms for decades, with only modest advancements made in the field compared with other genitourinary diseases. Therefore, a considerable unmet need remains for additional treatment options with enhanced activity and minimal toxicity for patients with advanced RCC. Simultaneous bispecific targeting of PD-1 and VEGF may improve efficacy and safety compared with combination therapy of PD-1- and VEGF-targeting single agents. In this podcast, authors discuss the evolving treatment landscape for patients with RCC and describe how bispecific antibodies, as monotherapy or combination therapy, have the potential to transform the treatment of these patients. Preclinical evidence shows that bispecific co-targeting of PD-(L)1 and VEGF may result in cooperative binding, which can enhance both PD-1 binding affinity and anti-angiogenic activity. Bispecific targeting can also potentially confer safety advantages owing to a reduction in immune-related adverse events. PD-(L)1/VEGF bispecifics under development include PF-08634404, ivonescimab, and BNT327, all of which have distinct structural configurations and mechanistic differences. These bispecific antibodies, among others, are being evaluated for the treatment of patients with advanced RCC. The authors discuss existing clinical evidence with bispecific antibodies in other cancers and explore the rationale for evaluating the antitumor activity of PD-(L)1/VEGF bispecifics, either as monotherapy or in conjunction with other treatments in patients with RCC. Podcast and Infographic available for this article. Infographic
Neuroendocrine carcinoma (NEC) is a rare, aggressive malignancy with limited treatment options and poor prognosis. We report a male patient diagnosed with a gastroenteropancreatic (GEP)-NEC with synchronous liver metastasis at the time of surgery who underwent a radical resection attempt. Despite radical-intent surgery followed by adjuvant carboplatin/etoposide, early recurrence developed with progression through multiple subsequent chemotherapy lines. During the treatment process, genetic profiling was performed twice to identify actionable genomic targets, with inclusion in the national IMPRESS study as a last resort. Comprehensive genomic profiling revealed TP53 mutation and RB1 loss but no actionable alterations. A patient-derived organoid (PDO) was successfully established from resected tumor tissue and retained key neuroendocrine and proliferative features, with partial genomic concordance to the primary tumor. Differences between the primary and subsequent PDO in variant allele frequencies suggest clonal selection during culture. Exploratory metabolomic profiling of tryptophan pathway metabolites in patient serum and PDO-culture media indicated tumor-associated metabolic alterations. We present clinical and translational efforts in difficult-to-treat NEC, illustrating both the translational challenges and the potential role of PDOs in advancing personalized treatment strategies for a cancer with very limited treatment options.
There is a dearth of head-to-head studies comparing covalent Bruton tyrosine kinase (cBTK) inhibitors in adults with chronic lymphocytic leukemia (CLL). Real-world evidence may complement clinical trial data by assessing relative effectiveness in routine practice. This retrospective observational study used a de-identified Medicare Fee-For-Service database to compare real-world outcomes associated with first-line cBTKi monotherapies in older adults with CLL. Patients aged ≥ 65 years with CLL initiating first-line ibrutinib, acalabrutinib, or zanubrutinib monotherapy between January 1, 2020 and September 30, 2025 were included. Real-world time to treatment discontinuation (rwTTD), time to next treatment (rwTTNT), and overall survival (rwOS) were evaluated using Kaplan–Meier analyses and Cox proportional hazards models. Subgroup analyses were performed by age group. Among 10,523 patients included, 3006 (28.6
Comprehensive genomic profiling (CGP) enables identification of patients eligible for targeted treatments, making it essential in the management of advanced cancer. This retrospective real-world study compared actionable mutations in CGP-tested patients with advanced/metastatic solid tumors to those who received single-gene/small-panel (SP) tests. Patients aged > 18 years with advanced/metastatic solid tumors (including non-small cell lung cancer (NSCLC), colorectal cancer, prostate cancer, breast cancer, or melanoma) with a CGP or SP test reported between 1 January 2018, and 31 December 2022, were included. OncoKB-derived actionability was compared between the two cohorts. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline characteristics. A weighted generalized linear model with log link was used to report actionability ratio (AR) and 95
Polypharmacy is common in patients with advanced urothelial carcinoma (UC) receiving avelumab maintenance therapy, raising concerns about potential drug–drug interactions (DDIs). We retrospectively analyzed patients enrolled in the multicenter MALVA study treated with avelumab maintenance. Concomitant medications were assessed using the Drug Interaction and Pharmacogenomics Information Network (Drug-PIN®). Drug-PIN® scores were calculated with and without avelumab and correlated with overall survival (OS) and progression-free survival (PFS). Among 115 patients, Drug-PIN® scores showed wide inter-patient variability but were not significantly influenced by inclusion of avelumab. No significant differences in OS or PFS were observed across Drug-PIN® risk categories. In this real-world cohort, polypharmacy and Drug-PIN® score did not impact survival outcomes, suggesting that, within the limitations of this exploratory analysis, Drug-PIN®-assessed DDI burden was not associated with survival outcomes in patients receiving avelumab maintenance therapy.
Hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2–) breast cancer comprises approximately 70
Bladder cancer (BC) is the most common malignancy of the urinary tract, with more than 75
Evidence guiding the optimal sequencing of later-line systemic therapy in advanced soft tissue sarcoma (STS) remains limited. The aim of this study was to identify prognostic factors for overall survival (OS) beyond second-line treatment and to explore therapy sequencing in routine clinical practice. A total of 90 patients with advanced STS receiving third-line or later systemic therapy were retrospectively analyzed. Extreme gradient boosting (XGBoost) was used to identify clinical predictors of 1-year OS. The most influential variables were subsequently evaluated in multivariable Cox models for OS from the start of third- and fourth-line therapy. Sequencing analyses compared OS according to the line of administration of commonly used later-line agents. In the third-line cohort (n = 88), inferior OS was independently associated with progression on second-line therapy (hazard ratio [HR] 2.31, p = 0.005). In contrast, lipo-/leiomyosarcoma histology was associated with improved survival (HR 0.37, p = 0.002), as was a time to progression ≥ 12 months on first-line therapy (HR 0.43, p = 0.007). Findings were largely consistent in the fourth-line cohort (n = 57). Sequencing analyses suggested sustained activity of trabectedin in later lines (p = 0.023), greater benefit of earlier pazopanib use (p = 0.022), and no significant impact of treatment line for gemcitabine + docetaxel combination therapy (p = 0.12). Machine learning-guided variable selection identified clinically relevant predictors of survival in later-line STS. Prior treatment response and histology strongly influence outcomes, and exploratory sequencing analyses suggest differential timing effects across systemic therapy agents.
Salivary duct carcinoma (SDC) is an aggressive neoplasm that typically involves the major salivary glands. This rapidly growing tumor is known to recur and metastasize to the neck nodes and to distant sites. Given its poor prognosis, researchers have focused on identifying factors and driver genomic alterations that may account for its behavior, ultimately yielding potential therapeutic targets. This review summarizes the growing body of knowledge on SDC since the publication of the latest WHO Classification of Tumors of the Head and Neck. Updates on emerging subtypes, immunohistochemical profiles, molecular alterations, and potential therapeutic targets are succinctly presented. Findings from studies on tumor immune microenvironment (TIME), which may have implications for the treatment and prognosis of SDC, are also discussed in this narrative review.
Cancer cells rewire their metabolism toward aerobic glycolysis (the Warburg effect), leading to lactate production that supports tumor growth, hypoxia adaptation, and immune evasion. In this context, syrosingopine, originally developed as an antihypertensive drug, has been repurposed as a dual inhibitor of the lactate transporters MCT1 and MCT4. This dual blockade promotes intracellular lactate accumulation, perturbs NAD+ regeneration, and can induce bioenergetic stress, particularly when combined with mitochondrial metabolic inhibitors. Despite encouraging preclinical data, critical gaps remain regarding immunometabolic remodeling and clinical translation. This narrative review summarizes the repositioning of syrosingopine as a metabolic modulator in oncology, emphasizing mechanistic insights, preclinical efficacy, synthetic lethality with metabolic inhibitors, immunometabolic effects, and considerations for clinical development. We conducted a narrative review of English-language publications on syrosingopine from 2016 to 2026, identified through PubMed and Scopus and supplemented by manual reference screening. Eligible studies investigated syrosingopine in the context of cancer biology, tumor metabolism, immunometabolism, therapeutic mechanisms, nanoformulations, or computational repurposing. Preclinical studies indicate that syrosingopine inhibits lactate efflux, reduces glycolytic flux, and depletes NAD+, thereby sensitizing cancer cells to biguanides such as metformin and to mitochondrial pyruvate carrier inhibitors such as UK-5099 through a synthetic lethality-like mechanism, inducing apoptosis and cell-cycle arrest. Advanced delivery systems enhance intratumoral drug accumulation, amplify metabolic stress, and remodel the immunosuppressive tumor microenvironment. At the same time, emerging data highlight context-dependent toxicities, including potential exacerbation of liver fibrosis and cardiovascular effects, which may constrain the therapeutic window. Syrosingopine exemplifies a preclinical “lactate trap”-based metabolic intervention with the potential to modulate integrated stress responses and immunometabolic pathways in glycolysis-dependent tumors. Its successful clinical repurposing will require biomarker-guided early-phase trials, optimization of nanoformulations and dosing strategies, incorporation of metabolic imaging readouts, and careful safety monitoring to address tissue-specific toxicities and metabolic plasticity. Graphical abstract available for this article.
Introduction Interindividual variability in the efficacy and toxicity of 6-mercaptopurine (6-MP) and methotrexate (MTX) drugs remains a major challenge in the treatment of pediatric acute lymphoblastic leukemia (ALL). Germline variation in pharmacogenes involved in drug metabolism, transport, and folate pathways may contribute to this variability. Methods In this retrospective cohort study, 43 pediatric patients with ALL treated at a tertiary referral center in Croatia according to ALL IC-BFM 2002 or 2009 protocols were genotyped for eleven variants in TPMT, ITPA, NUDT15, PACSIN2, MTHFR, TYMS, SLC19A1, and SLCO1B1 genes. Associations with average 6-MP dose during maintenance therapy, MTX pharmacokinetics during consolidation and MTX-related toxicity were analyzed. A polygenic risk score (PRS) was constructed to assess cumulative genetic risk of developing toxicity when administering these two drugs. Results Carriers of the ITPA rs1127354 variant required significantly lower average 6-MP doses compared with wild-type carriers. The NUDT15 rs61973267 variant was associated with higher tolerated 6-MP doses after exclusion of outliers. No significant associations were observed between individual variants and MTX clearance. A trend toward reduced risk of oral mucositis was observed in carriers of the SLCO1B1 rs4149056 variant. PRS analyses that included carriers of the TPMT rs1142345 and ITPA rs1127354 variants showed a borderline association with the requirement for 6-MP dose reduction. Conclusions Our findings support a role for ITPA and NUDT15 variants in modulating 6-MP dose requirements, while single-variant associations with MTX pharmacokinetics and toxicity were limited and not supported. These results underscore the complexity of antimetabolite pharmacogenetics and suggest that integrative polygenic approaches may better capture clinically relevant pharmacogenetic risk.
INTRODUCTION:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, requiring a multidisciplinary approach for effective management. The MDT Project aimed to define and pilot a structured care model for HCC management in Italy, supported by the implementation of integrated care pathways (ICPs), to standardize organizational processes and ensure the organizational requirements needed for appropriate patient management. METHODS:A multi-phase approach included a narrative review, semi-structured interviews with national experts, and the development of an optimal care model operationalized through a maturity model with 15 organizational elements. A total of 13 hospitals, selected to reflect national heterogeneity, participated in a pilot phase involving tailored action plans and hospital-specific ICPs. In total, ten hospitals proceeded to ICP implementation, and eight achieved certification by an external accreditation body. An expert consensus meeting subsequently validated the care model, key performance indicator (KPI) panel, and assessment tools. Organizational changes were assessed pre- and post intervention through the maturity model evaluation and a survey capturing clinicians' perceptions. RESULTS:Organizational improvements were observed primarily in areas directly targeted by the action plans, including the formalization of care-flow processes, multidisciplinary team structuring, case management, and coordination processes. More limited progress was seen in information systems and KPI monitoring, which require structural investments. Clinicians perceived the certification process as helpful in consolidating procedural standardization and documentation quality. CONCLUSIONS:The MDT Project piloted an organizational model for HCC management in Italy, focusing on care-pathway governance, multidisciplinary coordination, and center readiness. These findings represent an initial step toward broader implementation; future phases should incorporate clinical outcomes and patient-reported measures to evaluate the model's long-term impact.
Patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC) and pelvic lymph node dissection (PLND) often receive perioperative systemic therapy. However, treatment patterns are evolving with the advent of adjuvant immunotherapy. We examined recent trends in perioperative treatment management in a contemporary cohort of US patients with MIBC undergoing RC in the immunotherapy era. We conducted this retrospective, real-world study utilizing N-Power Medicine’s Bladder Analytical Dataset to describe demographics, clinical characteristics, and treatment patterns among patients with MIBC who underwent RC between 2021 and 2023. Treatment patterns were further stratified by pathologic high risk of recurrence following RC (ypT2-T4a orypN+; pT3-4a or pN+). A total of 138 patients with MIBC who underwent RC were included. The majority were male (82
Metabolic disorders are risk factors for hepatocellular carcinoma (HCC) through complex proinflammatory, molecular, and cellular processes within a systemic dysmetabolic milieu. Despite significant advancements in the last two decades, HCC remains a challenging condition to treat. Resmetirom is a liver‑directed, selective THR‑β agonist that enhances mitochondrial β-oxidation, reduces de novo lipogenesis, improves lipid and cholesterol homeostasis, and, in preclinical HCC associated with metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH-HCC) models, attenuates midkine/lipoprotein receptor-related protein 1 (MDK/LRP1)-mediated immunosuppressive crosstalk. In this article, we discuss the possibility and rationale for repurposing Resmetirom, which has recently been approved for the treatment of MASH, to potentially suppress MASLD/MASH-HCC. This discussion considers the evolving epidemiology of HCC, the ongoing challenges in HCC treatment, and the intricate connection between thyroid hormone signaling, MASLD, and HCC.
