The absence of haptic feedback has been a fundamental limitation of robotic surgery. The da Vinci 5 (dV5) system is the first da Vinci platform to incorporate true force feedback (FFB), enabling real-time transmission of instrument-tip forces to the surgeon. However, the quantitative impact of FFB sensitivity settings remains unclear. This study represents the first Japanese clinical evaluation of dV5 FFB in colorectal surgery.

We conducted a case-series analysis of 10 consecutive robotic colorectal cancer resections performed using the daV5 system by a single Japan Society for Endoscopic Surgery-certified surgeon. Instrument-tip force data (Newtons) from the first arm were extracted from system logs. Average forces were analyzed according to FFB sensitivity settings. Analyses were descriptive given the small sample size.

Under the medium sensitivity setting, the overall mean instrument-tip force was 1.68 N. Mean forces increased stepwise as sensitivity decreased: high 1.40 N, medium 1.68 N, low 2.60 N, and off 2.70 N, demonstrating a clear dose-dependent relationship (off/low > medium > high). Left-sided and rectal procedures tended to require slightly higher forces than right-sided colectomy. Transient force peaks were mainly attributable to instrument interference. No tissue injury was identified on video review.

FFB in the dV5 system may enable quantitative, sensitivity-dependent modulation of instrument-tip force during colorectal surgery. FFB reduced applied forces in a dose-dependent manner, supporting its role as a force-control mechanism rather than merely a sensory adjunct. However, its impact on tissue handling and clinical outcomes remains unclear, given the absence of grasping force evaluation.

Colorectal cancer (CRC) remains one of the most common malignancies in the Czech Republic. Despite advances in surgical treatment, the risk of recurrence persists, mainly due to minimal residual disease (MRD). Current surveillance strategies, including colonoscopy, CT imaging, and serum tumor markers (CEA, CA19-9), demonstrate limited sensitivity and specificity. In recent years, circulating tumor DNA (ctDNA) has emerged as a promising biomarker with significant prognostic and predictive potential.

This review was prepared based on a systematic literature search in PubMed, Web of Science, ScienceDirect, Scopus, and clinicaltrials.gov covering the period 2005-2025. Observational studies, retrospective analyses, and randomized clinical trials evaluating the prognostic and predictive role of ctDNA in patients with CRC were included.

Available studies confirm that the presence of ctDNA after curative resection of CRC is a strong predictor of early recurrence and worse survival, whereas ctDNA negativity reliably identifies patients at low risk. Prospective projects (VICTORI, GALAXY, COSMOS) demonstrated that ctDNA can predict relapse several months earlier than standard methods. The BESPOKE CRC study highlighted that only patients with positive ctDNA significantly benefit from adjuvant chemotherapy. The randomized DYNAMIC trial proved that a ctDNA-guided approach enables safe de-escalation of adjuvant therapy without compromising outcomes. Ongoing studies (PEGASUS, SAGITTARIUS, TRACC, DYNAMIC-III, ALTAIR, VEGA) are testing the efficacy of escalation and de-escalation strategies.

ctDNA is a highly promising biomarker for early MRN detection, risk stratification, and the individualization of adjuvant therapy in CRC patients. Its implementation in routine clinical practice, however, requires confirmation from ongoing randomized trials and validation in the Czech setting, where the use of ctDNA currently remains limited primarily to research.

Ewing sarcoma belongs to the family of undifferentiated small round cell sarcomas of bone and soft tissue. It is characterized by a gene fusion involving EWSR1 and an ETS-family transcription factor gene. In 85-96% of cases, a specific chromosomal translocation results in the EWSR1-FLI1 fusion gene, whose product functions as an oncogene essential for tumorigenesis. Ewing sarcoma is most common in adolescents and young adults. It primarily affects the diaphyses of long bones, the pelvis, and the axial skeleton, although extraosseous involvement is not uncommon. This is a highly malignant neoplasm, and in most cases, micrometastases are already present at the time of diagnosis. The treatment is multimodal and includes local therapy (surgery and/or radiotherapy) and systemic chemotherapy. One of the greatest therapeutic challenges remains the long-term systemic control of the disease. To improve overall survival - especially in high-risk patients - innovative treatment strategies are essential, as the potential for intensifying chemotherapy has reached its limit due to treatment-related toxicity. Both diagnostic and therapeutic management should take place in specialized sarcoma centers.

This article aims to provide an up-to-date overview of current diagnostic and therapeutic approaches in Ewing sarcoma.

Lymphoid neoplasms are a diverse group of cancers derived from lymphocytes, with classification recently updated by the 5th edition of the WHO Classification of Haematolymphoid Tumours (WHO-HAEM5). Benzene, a well-known carcinogen, is widely used in industries and environmental exposures vary; however, its association with specific lymphoid neoplasm subtypes remains unclear due to historical classification challenges. This study aimed to clarify the risk of lymphoid neoplasms related to benzene exposure using the updated WHO-HAEM5 framework.A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible studies were comparative human studies evaluating benzene exposure and lymphoid neoplasm risk, with sufficient data for risk estimates. Inclusion criteria specified study designs, participants, exposures and outcomes based on clinical diagnoses. Data were independently extracted by multiple reviewers. The main outcome was risk of lymphoid neoplasms and subtypes analysed by random-effects meta-analysis with heterogeneity and bias assessments.From 1488 records, 95 studies met criteria (65 occupational and 30 environmental exposure). Benzene exposure significantly increased overall lymphoid neoplasm risk (RR 1.26; 95% CI 1.18 to 1.35). B-cell neoplasms showed elevated risk (RR 1.26; 95% CI 1.16 to 1.37), including mature B-cell neoplasms, Hodgkin lymphoma and plasma cell neoplasms. T-cell and natural killer cell neoplasm risk was not significantly increased overall. Occupational exposures conferred higher risks with lower heterogeneity than environmental exposures.Benzene exposure is strongly associated with increased risk of lymphoid neoplasms, particularly B-cell subtypes, supported by the refined WHO-HAEM5 classification reducing heterogeneity. This study underscores the importance of biologically informed disease classification and the need for targeted occupational safety and environmental health policies.The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (Registration ID: CRD420251063844).

Cancer-associated fibroblasts (CAFs) are one of the main components of the tumor microenvironment (TME) of solid tumors. They have several functions, which all contribute to tumor growth and immune evasion. CAF presence is associated with poor clinical response to standard therapy and immunotherapy. However, its heterogeneity blunts their understanding and functionality. New analytical techniques are being applied to better understand their role in cancer. Meanwhile, CAF stratification and their immunomodulatory capabilities are the scope of many studies, also in the context of ionizing irradiation. In that regard, new immunotherapy strategies have set their sights on targeting CAF to modulate the TME into a more immune-stimulating environment. Among the different approaches, CAF depletion, reprogramming, and CAF-directed antibodies and cytokines can be distinguished, supported by substantial preclinical evidence and encouraging, but still preliminary clinical findings, mainly from early-phase (phase I) trials. Additionally, CAF-directed radionuclides have gained interest and are in clinical trials for therapeutic as well as diagnostic purposes. Here we summarize the studies and clinical developments of CAF-targeted therapies alone and in combination with radiotherapy.

The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib delays disease progression in dedifferentiated liposarcoma (DDLPS) by inducing tumor cell quiescence or senescence, though most tumors ultimately progress. Preclinical data suggest CDK4/6 inhibition enhances intratumoral inflammation and may synergize with immune checkpoint inhibitors.

This non-randomized, open-label, phase 2 study was conducted at Memorial Sloan Kettering Cancer Center. Patients with metastatic or unresectable DDLPS, or those expected to benefit from systemic therapy prior to surgery, were eligible. Patients received palbociclib (125 mg orally, days 1-21 of a 28-day cycle) plus retifanlimab (500 mg intravenous flat dose every 4 weeks). The primary endpoint was to assess the best objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

30 patients were treated and evaluable. Median age was 61 years (range 36-81), 67% were male, and 63% were treatment-naive. The median follow-up was 14.8 months. ORR was 20% (95% CI 8% to 39%) and the clinical benefit rate was 53% (95% CI 34% to 72%). Median progression-free survival and overall survival were 4.8 (95% CI 1.71 to 15.7) and 27 months (95% CI 21.7 to not reached (NR)), respectively. Median duration of response was 18.4 months (95% CI 9.4 months to NR). Grade ≥3 treatment-related adverse events occurred in 61% of patients, including one Grade 4 neutropenia. There were no Grade 5 events. Retifanlimab and palbociclib were discontinued due to toxicity in 23% and 17% of patients, respectively. Tumor sequencing identified JUN amplification in 6 of 14 patients with progressive disease versus 2 patients with stable disease or partial response. Patients with progressive disease had a higher median copy number alteration burden compared with those with stable disease or partial response.

Palbociclib plus retifanlimab demonstrated deep and durable responses in a subset of patients with advanced DDLPS, with an ORR exceeding that historically observed with either agent alone. Adverse events were generally manageable. Copy number alteration burden and JUN amplification merit further evaluation as potential biomarkers of resistance.

https://clinicaltrials.gov/study/NCT04438824.

Grade group 5 (GG5) prostate cancer (PCa) carries a less favorable prognosis after standard-of-care (SOC) therapy, necessitating novel therapeutic approaches. High-dose rate brachytherapy (HDRBT) and androgen deprivation therapy (ADT) may modulate immune response in GG5 PCa, particularly in tumors with increased immune content. This study evaluated whether the addition of nivolumab to SOC was associated with improved disease control in patients with high-volume GG5 PCa, including those with oligometastatic disease.

In this non-randomized phase II trial, 31 patients with localized or oligometastatic GG5 PCa and >30% positive biopsy cores were evaluated between September 2018 and April 2021. Patients received four doses of nivolumab (240 mg every 2 weeks) beginning 4 weeks prior to HDRBT, alongside ADT, HDRBT, and external beam radiation. The primary endpoint was to evaluate whether the 2-year freedom from biochemical recurrence (FFBR) rate would exceed a prespecified historical control rate of 75%.

Among the 31 patients, the median follow-up was 38.8 months (IQR 31.0-46.5 months). The addition of nivolumab to SOC RT with ADT was associated with a 2-year FFBR rate of 90.3% (95% CI 74.3% to 98.0%) (median FFBR not reached), exceeding the prespecified historical control rate of 75% (one-sided p value from binomial test=0.024). Definitive and probable nivolumab-related toxicity included 6.3% acute grade 2 and 6.3% acute grade 3 adverse events (AEs), with no grade 4+ AEs observed. A higher Decipher immunosuppression score at diagnosis correlated with early pathologic response (p=0.005) and was independently associated with time to metastatic failure (p=0.044).

Nivolumab combined with SOC was associated with encouraging FFBR in this high-risk GG5 PCa population and may represent a promising therapeutic intensification strategy. The Decipher immunosuppression score may serve as a predictive biomarker for response. These findings warrant further investigation in randomized trials.

Ductal carcinoma in situ (DCIS) is a preinvasive form of breast cancer. Current treatment consists of surgery, radiation, and often systemic therapy exposing patients to unnecessary health risks. Vaccines targeting DCIS may be a way to intercept preinvasive lesions and prevent the development of invasive breast cancer.

We developed a Th1 selective multiantigen, polyepitope plasmid-DNA vaccine encoding segments of IGFBP-2, HER2, and IGF-IR, all antigens expressed in hormone receptor positive and negative DCIS. We then performed a Phase I study in participants with non-metastatic breast cancer with no evidence of disease. The primary objective was to assess the safety of 3 monthly intradermal doses (150, 300, or 600 µg) of the tri-antigen vaccine with granulocyte macrophage colony-stimulating factor as an adjuvant. 32 participants were enrolled, 10 per dose level. Toxicity evaluations occurred monthly with vaccination and at 1 and 6 months after the last vaccine. Blood was collected at baseline and at 1 and 6 months after the last immunization to assess cellular immune responses. Participants were followed annually for 5 years for long-term toxicity.

There was no significant difference in adverse events (AEs) across dose levels and all related AEs were grades 1 or 2. All doses were immunogenic; responders included 70% of participants at the 150 µg dose level, 67% at the 300 µg dose, and 40% at the 600 µg dose level. All participants at the 300 µg dose retained significant Th1-antigen-specific immune response at 6 months after end of immunizations. T-cells derived from vaccine immunologic responders exhibited gene expression profiles that indicated an increased metabolic fitness as compared with immunologic non-responders.

The tri-antigen vaccine appears safe and immunogenic. The intermediate dose (300 µg) was chosen as the Phase II dose due to the long-term persistence of immunity after vaccination. The vaccine will be studied in Phase II trials for the treatment of DCIS.

NCT02780401.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality worldwide. While immune checkpoint blockade has revolutionized the treatment of many cancers, responses in HCC remain limited. Robust functional platforms capable of predicting individual responses to immunotherapy are urgently needed. In this study, we developed a patient-derived organotypic tumor spheroid (PDOTS) model that preserves the heterogeneity and immune microenvironment of HCC, enabling rapid and reliable assessment of targeted and immunotherapeutic responses.

Tumor tissues from 30 HCC patients were processed using a "Five-Point Clock" sampling method and cultured within a three-dimensional microfluidic chip supplemented with IL-2 and CD3/28 activator to maintain tumor-infiltrating lymphocyte activity. The genomic, immune, and histopathological fidelity of PDOTS relative to parental tumors was evaluated. Drug responses were assessed ex vivo and validated in matched patient-derived xenograft (PDX) models. Transcriptomic profiling was subsequently performed to identify gene signatures associated with treatment sensitivity and to construct a transcriptomic predictive model.

The PDOTS retained ≥60% viability over 7 days and faithfully maintained the genomic, immune, and histopathological profiles of parental tumors. Functionally, PDOTS exhibited immune-dependent responses to PD-1 blockade and predicted treatment responses with 80% concordance in matched PDX models. Transcriptomic profiling revealed distinct metabolic and immune signatures in sensitive and resistant tumors, which were used to derive the "Organoid Killing Index (OKI)". The OKI gene-derived index, a composite index integrating the enrichment scores of gene signatures associated with the OKI, strongly correlated (R=0.829, p<0.001) and predicted clinical outcomes in an external patient cohort treated with atezolizumab plus bevacizumab.

These findings establish PDOTS as an immune-competent ex vivo platform for functional precision oncology and support the integration of functional testing with transcriptomic prediction to guide individualized immunotherapy in HCC.

A woman in her 30s presented with irregular vaginal bleeding and abdominal distension. Initial imaging suggested a uterine fibroid; however, intraoperative findings during planned laparotomy were atypical, prompting an excisional biopsy. The initial pathological diagnosis was endometrial stromal sarcoma, and staging imaging suggested liver metastases, prompting chemotherapy initiation. One month later, she developed urinary retention, oedema and dyspnoea. Imaging revealed a large pelvic mass causing bilateral hydronephrosis, extensive lymphadenopathy and tumour lysis syndrome, managed with stents and supportive care. Re-evaluation of the biopsy established the diagnosis of primary endometrial diffuse large B-cell lymphoma (DLBCL). Hepatitis B positivity delayed chemotherapy; interim dexamethasone provided relief. Intensive chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and methotrexate/ifosfamide, etoposide and cytarabine resulted in a rapid response but was complicated by neutropenic sepsis, leading to death. This case highlights the diagnostic challenge of endometrial DLBCL, the critical importance of pathological re-evaluation and the need for careful toxicity monitoring during intensive chemotherapy.