Most novel anti-cancer therapies involve combining multiple immuno-oncology and/or targeted drugs. The historical paradigm of exploring combination regimens only after approval of the individual drugs is changing rapidly leading to clinical development of 'novel-novel' combination therapies consisting of at least two investigational agents.

Initiating those combination efforts early in development is an important strategy to accelerate evolution of the standard of care for high unmet need cancer indications. However, there are specific challenges associated with such development programs, with additional complexity if more than one company is involved. Representing a consortium of major oncology drug developers, we critically discuss those challenges and suggest potential solutions to encourage the development of novel multi-company combination therapies for solid and hematological tumors. The areas covered include trial strategies for early and late clinical development, including dose/regimen optimization, statistical considerations, optimizing safety profiles, dose modification approaches, contribution of components, choice of standard of care backbone and comparator regimens as well as regulatory strategies.

To assess the benefit of the new 'SURC' model, allowing patients having systemic anti-cancer therapy (SACT) to be seen acutely for assessment of adverse events, as well as scheduled early review in their treatment course. It also assessed the effect of the COVID-19 pandemic on this service.

Data was collected prospectively between 2020 and 2023 and then analysed retrospectively. The clinic was implemented at Ballarat Regional Integrated Cancer Centre (BRICC). It also included two outreach sites: Primary outcomes were the number of interactions by patients with SURC; secondary outcomes included the number of admissions, type of cancer involved, and reasons for contacting SURC.

This study demonstrated benefit for patients with cancer from a regional area who presented with acute complications of their treatment. Presentations requiring hospital admissions and further assessment in ED were lower compared to the pre-SURC period, with most patients being treated comprehensively in the SURC environment. The study demonstrated the utility of early SACT review as there was a decrease in the number of treatment disruptions due to early recognition of complications of each patient's regimen. There was also a gradual increase in patient presentations to the clinic during the duration of the study, reflecting the growing awareness and confidence in the service from both healthcare providers and patients alike.

This study demonstrates the benefit of the novel SURC model to patients living in regional areas with cancer who either develop acute complications or are routinely reviewed early during their course of treatment. Although this study was limited to only one public health service provider, we feel this new proactive paradigm for acute cancer care will become increasingly adopted across Australia, given its proven ability to look after patients undergoing SACT more efficiently in addition to reducing hospital admissions.

Esophageal cancer is a global burden, and multiple international societies exist to address the issue in international collaboration. This study aims to analyze the characteristics of esophageal cancer and robot-assisted minimally invasive esophagectomy (RAMIE) across geographic areas. We performed a retrospective analysis of the Upper GI International Robotic Association (UGIRA) international database from January 2016 to April 2024. Forty centers worldwide that were known to perform RAMIE were involved in establishing this consortium. The patient characteristics, surgical techniques, and short-term outcomes of RAMIE were compared by each regional area (Europe, Asia, North America, and South America). A total of 3,916 RAMIE cases were registered in the UGIRA database (2,643 in Europe, 1,130 in Asia, 111 in North America, and 32 in South America). The median age was 66 years, and 80.5% of patients were male. Notably, Asia had a high prevalence of squamous cell carcinoma (91.2%) and predominant use of the McKeown approach (94.9%). BMI was lower in Asia, whereas comorbidities were more common in Western countries across all types. The use of neoadjuvant chemotherapy and radiation was lower in Asia (48.2% and 20.8 %, respectively). Postoperative complications also differed by region; pneumonia was most common in Europe and South America, cardiopulmonary complications in North America, and recurrent nerve injury in Asia. In conclusion, regional differences were observed in baseline characteristics, treatment approaches, and complication patterns in patients treated by RAMIE for esophageal cancer. Recognizing these variations is essential for fostering mutual understanding and advancing the field through international collaboration.

Accurate assessment of submucosal invasion depth in pT1b-SM esophageal squamous cell carcinoma (ESCC) is critical to determine the need for additional treatment after endoscopic resection (ER). However, the reliability of submucosal invasion depth measurement has not been sufficiently validated. This study aimed to evaluate interobserver agreement in measuring invasion depth and to identify a reliable and reproducible assessment method.

Thirty-four pT1b-SM ESCC specimens obtained by ER were independently assessed by three pathologists. Invasion depth was measured using three methods on hematoxylin and eosin (H&E)- and desmin-stained slides: Method 1, from an imaginary line representing the original level of the muscularis mucosae; Method 2, from a reconstructed trajectory based on disorganized muscularis mucosae; and Method 3, from a line connecting the lowest visible ends of the disrupted muscularis mucosae, with each method measuring perpendicular to the deepest point of invasion. The lesions were classified as pT1a-MM, pT1b-SM1 (≤200 μm), or pT1b-SM2 (>200 μm). Interobserver agreement was assessed using Fleiss' κ and intraclass correlation coefficients (ICC).

Moderate to substantial agreement was observed across all methods. Method 3 (κ = 0.678, ICC = 0.789) achieved the highest agreement on H&E-stained slides, whereas Method 2 (κ = 0.615, ICC = 0.801) on desmin-stained slides demonstrated comparable reliability.

A stepwise approach using Method 3 on H&E-stained slides as a first-line method and Method 2 on desmin-stained slides as a complementary option when the muscularis mucosae is disrupted or ambiguous demonstrated high interobserver agreement and may enhance reproducibility in routine pathological practice.

The aim of this study was to evaluate the safety and clinical benefits of adding concurrent radiotherapy to neoadjuvant chemoimmunotherapy in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). This multicenter retrospective study enrolled eligible ESCC patients treated between November 2019 and July 2020 from four hospitals. Baseline characteristics were collected, and patients were categorized into two groups based on neoadjuvant regimens: the chemoimmunotherapy group (CI group) and the chemoimmunotherapy with concurrent radiotherapy group (CIR group). Treatment-related complications, surgical outcomes, pathological response, tumor recurrence, and survival were analyzed. A total of 78 eligible patients were included: 49 in the CI group and 29 in the CIR group. Baseline characteristics (age, sex, clinical stage, cardiopulmonary function) were balanced between groups. During neoadjuvant therapy, the CI group had significantly lower incidences of grade 3 and grade 4 leukopenia/neutropenia (15/49 vs. 15/29, P = 0.025), and lower incidences of grade 3 and grade 4 checkpoint inhibitor pneumonitis (CIP) (1/49 vs. 8/29, P = 0.002). All CI group patients achieved R0 resection after 1-3 neoadjuvant cycles versus 24/29 in the CIR group (P > 0.05). The CIR group showed higher major pathological response (including pathological complete response) rates (16/24 vs. 10/49), though statistically non-significant (P = 0.121). No significant differences were observed in 5-year progression-free survival or overall survival. Adding concurrent radiotherapy to neoadjuvant chemoimmunotherapy increased hematologic toxicity and CIP in resectable locally advanced ESCC patients, without conferring survival benefits.

The main objective of dose finding trials is to find an optimal dose amongst a candidate set for further research. The trial design in oncology proceeds in stages with a decision as to how to treat the next group of patients made at every stage until a final sample size is reached or the trial stopped early. This work applies a Bayesian decision-theoretic approach to the problem, proposing a new utility function based on both efficacy and toxicity and grounded in von Neumann-Morgenstern (VNM) utility theory. Our proposed framework seeks to better capture real clinical judgments by allowing attitudes to risk to vary when the judgments are of gains or losses, which are defined with respect to an intermediate outcome known as a reference point. We call this method Reference Dependent Decision Theoretic dose finding (R2DT). A simulation study demonstrates that the framework can perform well and produce good operating characteristics. The simulation results demonstrate that R2DT is better at detecting the optimal dose in scenarios where candidate doses are around minimum acceptable efficacy and maximum acceptable toxicity thresholds. The proposed framework shows that a flexible utility function, which better captures clinician beliefs, can lead to trials with good operating characteristics, including a high probability of finding the optimal dose. Our work demonstrates proof-of-concept for this framework, which should be evaluated in a broader range of settings.

An 8-year-old neutered female Labradoodle presented with acute restlessness and inability to stand. Point-of-care ultrasound revealed a large abdominal mass, prompting further imaging. Computed tomography (CT) demonstrated a mass with marked mineralization, a thick, enhancing rim, and signs of intra-abdominal dissemination. Surgical excision of the mass was performed, and histopathology confirmed extraskeletal osteosarcoma (ESOSA) secondary to a retained surgical sponge (gossypiboma). Four months post-surgery, the dog developed pulmonary metastases and was euthanized. This report is the first to describe CT findings of ESOSA secondary to a retained surgical sponge in a dog.

Peripheral T-cell lymphomas are rare, aggressive malignancies with significant diagnostic challenges due to their heterogeneity.

This retrospective study analysed 43 nodal Peripheral T-cell lymphomas cases diagnosed between 2019 and 2024 at the Blood Transfusion Hematology Hospital in Southern Vietnam and reclassified them using the World Health Organization 2022 classification.

Nodal T-follicular helper cell lymphoma, angioimmunoblastic type, emerged as the most prevalent subtype (51.2%), markedly exceeding rates reported in Western (32.5%) and East Asian studies (36.2%). Despite the higher prevalence of Epstein-Barr Virus in Vietnam, the proportion of Epstein-Barr Virus positive in Peripheral T-cell lymphomas was not elevated (20%), suggesting additional genetic or environmental factors influencing lymphoma pathogenesis.

These findings underscore the critical role of updated diagnostic standards and the utility of advanced markers in improving Peripheral T-cell lymphomas classification. This study provides rare insights into Peripheral T-cell lymphomas pathology in Vietnam, contributing valuable data to the global understanding of these rare lymphomas.

Previous exposure to hepatitis B virus (HBV) may influence the risk of developing hepatocellular carcinoma (HCC) and other liver-related events (LRE), in particular in patients after HCV cure. Previous studies were not conclusive and there are only few large studies on this topic from Europe.

We analysed clinical endpoints (≥ 3-point increase in MELD score, oesophageal variceal bleeding, ascites, encephalopathy, liver transplantation, death, with/without HCC; HCC alone) in patients cured from HCV. Data were obtained from the German Hepatitis C Registry. Patients after organ transplantation, a history of HCC, HIV co-infection, or HBsAg positivity were excluded. A subanalysis was conducted in patients with cirrhosis. Statistical analyses included logistic regression to identify predictors of clinical endpoints and Kaplan-Meier curves to analyse the influence of HBV serological markers.

A cohort of 6198 patients fulfilled inclusion criteria, the median time of follow-up was 2.5 years (range 0.04-8.01). Serological evidence of previous HBV exposure was present in 1889 patients (anti-HBc positive). In patients with cirrhosis, univariate analyses identified anti-HBc positivity (odds ratio [OR], 1.48), cirrhosis (OR, 4.89), features of portal hypertension (ascites (OR, 5.66), oesophageal varices (OR, 4.88)), diabetes (OR, 3.23), and malignancies (OR, 10.34) as risk factors for composite LRE. In multivariable analysis, anti-HBc positivity (OR, 1.53) and cirrhosis (OR, 4.63) remained independent risk factors for the composite endpoints, whereas anti-HBc positivity was not associated with HCC or Kaplan-Meier survival analyses.

Resolved HBV infection was not associated with the development of HCC or survival in Caucasians after HCV cure. Although anti-HBc positivity was linked to composite outcomes, its clinical relevance appears limited.

The registry was registered at the German Clinical Trials Register (DRKS; IDDRKS00009717).

IntroductionWhile largely preventable, cervical cancer remains a major cause of morbidity and mortality in low- and middle-income countries (LMICs), where gaps in screening uptake persist despite expanding prevention efforts. In many patriarchal settings, men play influential roles in household decision-making and access to healthcare, positioning them as critical but under-engaged stakeholders. There remains limited understanding of how educational strategies to improve health literacy can be designed to effectively engage men in supporting women's screening participation.MethodsWe conducted a qualitative study in northern Ghana to explore men's understanding, priorities, and values related to cervical cancer prevention to inform male-focused educational strategies. Guided by the Consolidated Framework for Implementation Research and the Health Belief Model, 9 in-depth semi-structured interviews were conducted with married adult men recruited from community settings, examining household roles, perceptions of cervical cancer and screening, and preferences for education and engagement approaches. Interviews were conducted in English or Dagbani, audio-recorded, transcribed, and analyzed thematically using a hybrid inductive and deductive approach.ResultsThree cross-cutting themes emerged. Men viewed healthcare professionals as trusted sources of cervical cancer information and described their roles as primary financial decision-makers, with cost and competing household priorities influencing support for screening. Masculine responsibility, particularly related to fertility and family wellbeing, strongly motivated engagement, and messages framed around these themes were more compelling than disease-focused messaging alone. Participants recommended integrating education into routine health services, leveraging healthcare workers, offsetting screening-related costs, and using mass media to initiate awareness and information seeking.ConclusionMen represent pivotal yet underutilized partners in cervical cancer prevention. Educational strategies that align with men's roles, economic realities, and trusted sources of information and address household decision-making barriers may enhance screening uptake while supporting women-centered care. These findings provide implementation-relevant insights to inform male-engaged cervical cancer prevention strategies across diverse LMIC settings.