The purpose of this research was to evaluate the effectiveness and safety of neoadjuvant chemotherapy plus radical surgery (NCRS) and concurrent chemoradiotherapy (CCRT) based on three-dimensional conformal radiation therapy (3DCRT) for FIGO 2018 stage IB3/IIA2 patients with cervical squamous cell carcinoma in a resource-limited setting.

The clinical outcomes and incidence of complications in 137 patients who underwent NCRS with those of 163 patients who CCRT based on 3DCRT were compared. Propensity score matching (PSM) analysis was used to match the two groups to enable further statistical comparisons. Survival analysis was performed utilizing Cox proportional hazards regression analyses, Kaplan-Meier curves, and log-rank tests. Furthermore, the incidence of complications between the two groups was also compared using chi-squared tests.

PSM analysis identified 103 matched pairs of patients. The NCRS and CCRT groups exhibited 5-year overall survival (OS) rates of 85.4% and 91.2%, respectively (p=0.19). Additionally, the NCRS and CCRT groups exhibited 5-year disease-free survival (DFS) rates of 76.7% and 89.3% (p=0.02), and the recurrence rates were 20.4% and 9.7% (p=0.03), respectively. However, the CCRT group exhibited a higher incidence of early any-grade complications (79.6% vs 35.9%, p<0.001) and early grade 3 complications (15.5% vs 2.9%, p=0.002) compared to the NCRS group. In terms of overall late complications, there was no significant difference in the incidence between the two groups. Multivariate analysis revealed that stage IIA2 emerged as an independent risk factor for OS (aHR 8.89; p=0.033). Moreover, histologic grade 2-3 (aHR 5.3; p=0.022), stage IIA2 (aHR 2.95; p=0.043), NCRS treatment (aHR 2.41; p=0.012) were identified as independent risk factors for DFS.

In resource-limited settings, for patients with FIGO 2018 stage IB3/IIA2 cervical squamous cell carcinoma, 3DCRT-based CCRT offers superior disease-free survival and reduced recurrence rates compared to NCRS, despite increased early complication rates.

We investigated whether TK1 concentration or activity in the blood, drawn at baseline and under therapy, might have value for therapy management in 110 hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (mBC) patients treated with CDK4/6 inhibitors (CDK4/6i) and/or endocrine therapy (ET). TK1 concentration and activity were not significantly correlated with each other in matched samples. In the CDK4/6i cohort at baseline, high TK1 concentration and activity were significantly associated with a decreased PFS and primary resistance. Longitudinal sampling revealed a higher variability of TK1 concentration under therapy compared to TK1 activity that was reduced during therapy. Elevated TK1 activity after six months of CDK4/6i and an increase in TK1 concentration from baseline to six months under CDK4/6i significantly correlated with a decreased PFS. These results indicate a possible value of TK1 concentration and activity before and during CDK4/6i for HR+/HER2- mBC patients to guide treatment that warrants further investigation.

Carcinoembryonic antigen (CEA) is the only prognostic circulating biomarker used in clinical practice for recurrence free (RFS), progression free (PFS) and overall survival (OS) in patients with colorectal cancer (CRC). Not all CRC tumors express this protein and carbohydrate antigen (CA)19-9 has been proposed as an adjunctive in prognostication. We aimed to test if CA19-9 yielded additional information to CEA regarding prognosis.

We included 886 patients with CRC across eight clinical cohorts. Preoperative serum samples were collected from 376 patients with stage I-III CRC and from 510 with metastatic (m)CRC before 1st (n = 233), 3rd (n = 178) and 3rd/4th (n = 99) line chemotherapy. CA19-9 and CEA were determined by routine assays, the values were log-2 transformed and entered as variables in Cox regression models with RFS (stage I-III), PFS and OS as the outcomes, adjusted for age, sex, and site of primary tumor and mutual adjustment between CA199 and CEA. Random effects meta-analyses were conducted for stage I-III,1st line, and 3rd/4th line mCRC cohorts separately.

Meta-analyses showed that higher pre-treatment CA19-9 and CEA were associated with shorter RFS (CA19-9: hazard ratio per doubling of concentration (HR)=1.20, 95 % confidence interval (CI) 1.05-1.38; CEA: HR=1.22, 95 % CI 1.05-1.41) in stage I-III CRC. Only higher CEA was associated with shorter OS in 1st line mCRC (HR=1.07, 95 % CI 1.00-1.07).

CA19-9 might aid in identifying patients with a high risk of recurrence after primary radical resection. Further studies are needed to validate these findings.

Therapeutic efficacy of KRASG12C(OFF) inhibitors (KRASG12Ci) in KRASG12C-mutant non-small cell lung cancer (NSCLC) varies widely. The activation status of RAS signaling in tumors with KRASG12C mutation remains unclear, as its ability to cycle between the active GTP-bound and inactive GDP-bound states may influence downstream pathway activation and therapeutic responses. We hypothesized that the interaction between RAS and its downstream effector RAF in tumors may serve as indicators of RAS activity, rendering NSCLC tumors with a high degree of RAS engagement and downstream effects more responsive to KRASG12Ci compared with tumors with lower RAS-RAF interactions.

We developed a method for measuring in situ RAS binding to RAF in cancer samples using proximity ligation assays (PLA) designed to detect panRAS-CRAF interactions.

The panRAS-CRAF PLA signal correlated with levels of both RAS-GTP and phosphorylated ERK protein, suggesting that this assay can effectively assess active RAS signaling. We found that elevated panRAS-CRAF PLA signals were associated with increased sensitivity to KRASG12Ci in KRASG12C-mutant NSCLC cell lines, xenograft models, and patient samples. Applying a similar PLA approach to measure the interactions between EGFR and its adapter protein growth factor receptor-bound protein 2 as a surrogate for EGFR activity, we found no relationship between EGFR activity and response to KRASG12Ci in the same samples.

Our study highlights the importance of evaluating in situ RAS-RAF interactions as a potential predictive biomarker for identifying patients with NSCLC most likely to benefit from KRASG12Ci. The PLA developed for quantifying these interactions represents a valuable tool for guiding treatment strategies.

Eribulin can represent a therapeutic alternative for patients with advanced breast cancer who have received at least one or two lines of anthracyclines-based chemotherapy and taxane therapy. In this observational study, we focused on long-responder patients, i.e. with an objective response or stability ≥ 6 months under eribulin to better characterize them.

Metastatic breast cancer (MBC) patients treated by eribulin in 2nd, 3rd or 4th line between September 2011 and June-2018 were included. The following parameters were assessed: primary tumor and metastasis characteristics, type of response and duration, disease progression, treatment received, toxicities, progression free survival (PFS), overall survival (OS), and prognostic factors of OS and PFS. Special attention was paid to patients with hepatic disease (HD).

Among the 98 patients included, an analysis was conducted on 84 patients (median age 62). Median duration of response was 25.6 weeks (95 IC 22-27.7) with a median number of infusions of 6. Response was similar, irrespective of ERI line number. HD was observed in 70.2 % of patients. Median PFS was 9 months (95 %CI 8-10). Subgroup analysis showed similar PFS, irrespective of HD (p = 0.21) and treatment line (p = 0.46). Median OS was 24 months. (95 % IC 20-31). The main prognostic factors of OS were duration of response (p < 0.001) and, progesterone receptor positiveness was associated to PFS (p = 0.006).

This multicentric, retrospective study highlights eribulin as a potential second-line therapy for MBC with a median response duration of 25 weeks after 6 infusions. The safety and efficacy profiles align with previous studies, supporting its role as a viable treatment option. Notably, the response and PFS were independent of hepatic metastasis, suggesting benefit across various MBC subtypes, including those with liver involvement. However, the retrospective design warrants cautious interpretation, and further prospective studies are needed to confirm these findings and optimize eribulin's use, potentially through molecular profiling for personalized treatment strategies.

Our study aimed to examine the predictive relevance of the Systemic Immune-Inflammation Index (SII) in patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 113 mCRPC patients were assessed. In this descriptive study, SII was calculated using the formula (neutrophil count × platelet count)/lymphocyte count. The optimal threshold for SII, determined via the ROC curve, was 700. Patients with SII ≤ 700 were classified as SII-low, while those with SII > 700 were categorized as SII-high. The median overall survival (mOS) was significantly longer in the low SII group compared to the high SII group (*P = 0.015). In multivariate analysis, Gleason score, albumin levels, CHAARTED volume, and SII were identified as significant prognostic factors. Our findings indicate that SII has a strong correlation with survival and can serve as an independent prognostic marker in mCRPC patients.

Scientists have been actively investigating novel therapies that can effectively eradicate cancer cells with negligible side effects in normal tissues when used alone or in a combinatorial approach. Photodynamic therapy has emerged as a promising non-invasive therapy that integrates photosensitizer, oxygen, and a specific wavelength of light for the treatment of cancer. Despite encouraging outcomes yielded by PDT, conventional PSs are faced with longstanding challenges such as poor water solubility, a short half-life, and off-target toxicity. Development of nanotherapeutics has shown great potential in overcoming this issue. The tumor microenvironment is inherently hypoxic, and this promotes tumor resistance to PDT, as it is oxygen-dependent. Photoactivated chemotherapy, an oxygen-independent light-based therapy, utilizes chemotherapeutic regimens that remain inert until exposed to light, allowing target-specific activation while minimizing off-target toxicity. Integration of these techniques can improve selectivity and yield synergistic cytotoxic effects that could improve cancer treatment.

We aim to report on somatostatin receptor (SSTR)-targeted molecular imaging and therapy in patients with advanced esthesioneuroblastoma (ENB).

Five patients with ENB [Kadish stage D in 5/5 (100%); Hyams grade 2 in 2/5 (40%), grade 3 in 2/5 (40%), undetermined in 1/5 (20%)] underwent SSTR-directed PET/CT. We quantified SSTR-avid tumor volume (TV), maximum SUV (SUVmax), and target-to-background ratios (TBR). Based on imaging, peptide receptor radionuclide therapy (PRRT) along with dosimetry was also conducted. We recorded nephrotoxicity and hematotoxicity, including estimated glomerular filtration rate (eGFR), hemoglobin, leukocytes, and thrombocytes at baseline and after the last treatment cycle. We determined adverse events following Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Response and progression-free survival (PFS) was also evaluated.

All 5 patients were rated positive on SSTR-PET/CT. On a lesion-based level, we identified 32 SSTR-avid tumor sites with a median TV of 11.7±10.8 and SUVmax of 24.3±12.8. TBR was 19.8±9.7, indicating excellent image contrast. After median 4 (range, 2-6) cycles with a median of 7.7 GBq per cycle per patient, we observed no CTCAE grade 3 or 4 toxicity for leukocytes and thrombocytes and no significant CTCAE events for renal function. One patient (20%), however, developed reversible grade 3 anemia. Up to 11.8 Gy in tumor lesions were achieved. Partial response was recorded in 3/5 (60%), stable disease in 1/5 (20%), and progressive disease in 1/5 (20%). The median PFS was 29 weeks.

SSTR-directed PET provided high image contrast in ENB, suggesting good read-out capabilities in this tumor type. PRRT was also feasible, along with an acceptable safety profile, thereby rendering SSTR-targeted theranostics a potential treatment option in advanced disease.

Radiological follow-up of oncology patients requires the detection of metastatic lung lesions and the quantitative analysis of their changes in longitudinal imaging studies. Our aim was to evaluate SimU-Net, a novel deep learning method for the automatic analysis of metastatic lung lesions and their temporal changes in pairs of chest CT scans.

SimU-Net is a simultaneous multichannel 3D U-Net model trained on pairs of registered prior and current scans of a patient. It is part of a fully automatic pipeline for the detection, segmentation, matching, and classification of metastatic lung lesions in longitudinal chest CT scans. A data set of 5040 metastatic lung lesions in 344 pairs of 208 prior and current chest CT scans from 79 patients was used for training/validation (173 scans, 65 patients) and testing (35 scans, 14 patients) of a standalone 3D U-Net models and 3 simultaneous SimU-Net models. Outcome measures were the lesion detection and segmentation precision, recall, Dice score, average symmetric surface distance (ASSD), lesion matching, and classification of lesion changes from computed versus manual ground-truth annotations by an expert radiologist.

SimU-Net achieved a mean lesion detection recall and precision of 0.93±0.13 and 0.79±0.24 and a mean lesion segmentation Dice and ASSD of 0.84±0.09 and 0.33±0.22 mm. These results outperformed the standalone 3D U-Net model by 9.4% in the recall, 2.4% in Dice, and 15.4% in ASSD, with a minor 3.6% decrease in precision. The SimU-Net pipeline achieved perfect precision and recall (1.0±0.0) for lesion matching and classification of lesion changes.

Simultaneous deep learning analysis of metastatic lung lesions in prior and current chest CT scans with SimU-Net yields superior accuracy compared with individual analysis of each scan. Implementation of SimU-Net in the radiological workflow may enhance efficiency by automatically computing key metrics used to evaluate metastatic lung lesions and their temporal changes.

Background/Objectives: Transarterial chemoembolization (TACE) is a widely accepted and minimally invasive treatment for primary and metastatic liver cancer. Performing TACE with drug-eluting beads helps obtain a greater drug concentration in the target lesion, significantly reducing systemic drug leakage, liver toxicity, and adverse events. The aim of this study is to describe the safety and feasibility of TACE performed with BioPearlTM, the first biodegradable drug-eluting microspheres. Methods: This was a retrospective observational study on 13 consecutive patients affected by hepatocellular carcinoma (HCC) treated with doxorubicin-loaded-BioPearlTM-TACE. Data on safety, feasibility, and tumor response were collected. Results: One intra-procedural catheter blockage was registered, as well as two post-treatment bilomas that required additional treatment. No severe general drug-related side effects were detected at the follow-up. The 1-month overall disease control was 90.9%, with six complete responses. Conclusions: Data suggest that chemoembolization with BioPearlTM is feasible and safe for the treatment of HCC as indicated by good tolerability.

This study efforts to explore the association of adverse events (AEs) with efficacy in HER2-positive breast cancer patients treated with TDM1.

This retrospective study included women diagnosed with HER2+ BC treated with TDM1 from January 2012 to December 2023. Event-free survival (EFS) was the endpoint. Tumour response was assessed by disease control rate (DCR) and objective response rate (ORR). The chi-squared test, analysis of variance (ANOVA), Cox proportional hazards regression and Kaplan-Meier survival analysis was employed to evaluate the association of AEs with tumour efficacy.

A total of 48 women with a median age of 52 years (median follow-up 8.4 months) were included in the study. Among them, 33 patients (68.8%) experienced adverse events, including platelet depletion and liver function abnormalities, 3 patients (6.3%) discontinued TDM1 due to severe platelet depletion. The overall objective response rate (ORR) was 25.0% and the disease control rate (DCR) was 43.8%. Using the Chi-squared test, we found a statistically significant difference in ORR and DCR between patients who developed a platelet reduction and those who did not. DCR was significantly higher in patients with liver dysfunction than in those without. ANOVA showed that exposure to hepatic dysfunction and platelet reduction, lines of therapy, and treatment course were associated with EFS. In the Kaplan-Meier survival analysis, both liver dysfunction and platelet reduction were correlated with significantly longer EFS (p=0.033 and p=0.038, respectively).

This retrospective study demonstrated that AEs were associated with tumour efficacy in patients with HER2+ BC treated with TDM1.

To evaluate the clinical efficacy of nab-paclitaxel based chemotherapy in the treatment of advanced epithelioid hemangioendothelioma (EHE).

Since March 2022, chemotherapy has been recommended for patients with advanced EHE characterized by large tumors (liver tumors > 10 cm or tumors in other organs > 3 cm), rapid tumor progression, severe symptoms, serosal effusion, and treatment failure. Two chemotherapy regimens were administered: nab-paclitaxel plus bevacizumab and nab-paclitaxel plus sirolimus. Clinical data and outcomes were retrospectively analyzed.

From March 2022 to August 2024, 21 patients with histologically confirmed EHE who received nab-paclitaxel based chemotherapy were included. At baseline, 18 patients (85.7%) presented with tumor-related symptoms, and serosal effusion was detected in 12 patients (57.1%). Among patients with hepatic EHE, six (28.6%) had tumors > 10 cm, while six (28.6%) with EHE at other sites had tumors > 3 cm. Partial response and stable disease were achieved in 5 (23.8%) and 12 (57.1%) patients, respectively, resulting in a disease control rate of 80.9%. Symptom relief was observed in 15 of 18 patients (83.3%), and decreased serosal effusion was noted in 6 of 12 patients (50.0%). The 1- and 2-year progression-free survival rates were 50.7% and 13.5%, respectively, while the 1- and 2-year overall survival rates were 70.6% and 51.5%, respectively.

Nab-paclitaxel based chemotherapy may offer an effective treatment option for patients with advanced EHE exhibiting adverse prognostic factors. However, further clinical trials are required to confirm its efficacy.

Background/Objectives: Radiomic features exhibit a correlation with tumor size on pretreatment images. However, on post-treatment images, this association is influenced by treatment efficacy and varies between responders and non-responders. This study introduces a novel model, called baseline-referenced Delta radiomics, which integrates the association between radiomic features and tumor size into Delta radiomics to predict chemotherapy response in liver metastases from breast cancer (BC) and colorectal cancer (CRC). Materials and Methods: A retrospective study analyzed contrast-enhanced computed tomography (CT) scans of 83 BC patients and 84 CRC patients. Among these, 57 BC patients with 106 liver lesions and 37 CRC patients with 109 lesions underwent post-treatment imaging after systemic chemotherapy. Radiomic features were extracted from up to three lesions per patient following manual segmentation. Tumor response was assessed by measuring the longest diameter and classified according to RECIST 1.1 criteria as progressive disease (PD), partial response (PR), or stable disease (SD). Classification models were developed to predict chemotherapy response using pretreatment data only, Delta radiomics, and baseline-referenced Delta radiomics. Model performance was evaluated using confusion matrix metrics. Results: Baseline-referenced Delta radiomics performed comparably or better than established radiomics models in predicting tumor response in chemotherapy-treated patients with liver metastases. The sensitivity, specificity, and balanced accuracy in predicting response ranged from 0.66 to 0.97, 0.81 to 0.97, and 80% to 90%, respectively. Conclusions: By integrating the relationship between radiomic features and tumor size into Delta radiomics, baseline-referenced Delta radiomics offers a promising approach for predicting chemotherapy response in liver metastases from breast and colorectal cancer.

Colorectal cancer liver metastasis (CRLM) is a significant contributor to cancer-related illness and death. Neoadjuvant chemotherapy (NAC) is an essential treatment approach; however, optimal patient selection remains a challenge. This study aimed to develop a machine learning-based predictive model using hematological biomarkers to assess the efficacy of NAC in patients with CRLM.

We retrospectively analyzed the clinical data of 214 CRLM patients treated with the XELOX regimen. Blood characteristics before and after NAC, as well as the ratios of these biomarkers, were integrated into the machine learning models. Logistic regression, decision trees (DTs), random forest (RF), support vector machine (SVM), and AdaBoost were used for predictive modeling. The performance of the models was evaluated using the AUROC, F1-score, and external validation.

The DT (AUROC: 0.915, F1-score: 0.621) and RF (AUROC: 0.999, F1-score: 0.857) models demonstrated the best predictive performance in the training cohort. The model incorporating the ratio of post-treatment to pre-treatment gamma-glutamyl transferase (rGGT) and carcinoembryonic antigen (rCEA) formed the GCR index, which achieved an AUROC of 0.853 in the external validation. The GCR index showed strong clinical relevance, predicting better chemotherapy responses in patients with lower rCEA and higher rGGT levels.

The GCR index serves as a predictive biomarker for the efficacy of NAC in CRLM, providing a valuable clinical reference for the prognostic assessment of these patients.

In oncology trials, response evaluation criteria are pivotal in developing new treatments. This study examines the influence of measurement variability in brain lesions on response classification, considering long-standing cut-offs for progression and response were determined before the era of submillimeter resolutions of medical imaging.

We replicate a key study using modern radiological tools. Sixteen radiologists were tasked with measuring twelve near-spherical brain tumors using visual estimation (eyeballing), diameter measurements and artificial intelligence (AI) assisted segmentations. Analyses for inter- and intraobserver variability from the original were replicated. Additionally, we researched the effect of measurement error on the misclassification of progressive disease using a computer simulation model.

The combined effect of intra- and interobserver error varied between 13.6 and 22.2% for eyeballing and 6.8-7.2% for diameter measurement, using AI-assisted segmentation as reference. We observed erroneously declared progression (cut-off at 20% increase) in repeat measurements of the same tumor in 25.5% of instances for eyeballing and in 1.1% for diameter measurements. Response (cut-off at 30% decrease) was erroneously declared in 12.3% for eyeballing and in 0% for diameter measurements. The simulation model demonstrated a more pronounced impact of measurement error on cases with fewer total number of lesions.

This study provides a minimum expected measurement error using real-world data. The impact of measurement error on response evaluation criteria misclassification in brain lesions was most pronounced for eyeballing. Future research should focus on measurement error for different tumor types and assess its impact on response classification during patient follow-up.

Assessing the response to oncological treatments is paramount for determining the prognosis and defining the best treatment for each patient. Several biomarkers, including imaging, can be used, but standardization is fundamental for consistency and reliability. Tumor response evaluation criteria have been defined by international groups for application in pharmaceutical clinical trials evaluating new drugs or therapeutic strategies. RECIST 1.1 criteria are exclusively based on unidimensional lesion measurements; changes in tumor size are used as surrogate imaging biomarkers to correlate with patient outcomes. However, increased tumor size does not always reflect tumor progression. The introduction of immunotherapy has led to the development of new criteria (iRECIST, Level of Evidence (LoE) Ib) that consider the possibility that an increase in disease burden is secondary to the immune response instead of progression, with the new concept of Unconfirmed Progressive Disease (a first progression event which must be confirmed on follow-up). Specific criteria were devised for HCC (mRECIST, LoE IV), which measure only enhancing HCC portions to account for changes after local therapy. For GIST treated with imatinib, criteria were developed to account for the possible increase in size reflecting a response rather than a progression by assessing both tumor size and density on CT (Choi, LoE II). This article provides concise and relevant practice recommendations aimed at general radiologists to help choose and apply the most appropriate criteria for assessing response to treatment in different oncologic scenarios. Though these criteria were developed for clinical trials, they may be applied in clinical practice as a guide for day-to-day interpretation. KEY POINTS: Response evaluation criteria, designed for use in clinical trials, might serve as a surrogate biomarker for overall survival. RECIST 1.1 defines measurable and non-measurable disease among which target lesions and non-target lesions are selected at baseline as reference for follow-ups. Some therapies and/or cancers require the use of different criteria, such as iRECIST, mRECIST, and Choi criteria.

The patient-derived xenograft (PDX) model is a crucial in vivo model extensively employed in cancer research that has been shown to maintain the genomic characteristics and pathological structure of patients across various subtypes, metastatic, and diverse treatment histories. Various treatment strategies utilized in PDX models can offer valuable insights into the mechanisms of tumor progression, drug resistance, and the development of novel therapies. This review provides a comprehensive overview of the establishment and applications of PDX models. We present an overview of the history and current status of PDX models, elucidate the diverse construction methodologies employed for different tumors, and conduct a comparative analysis to highlight the distinct advantages and limitations of this model in relation to other in vivo models. The applications are elucidated in the domain of comprehending the mechanisms underlying tumor development and cancer therapy, which highlights broad applications in the fields of chemotherapy, targeted therapy, delivery systems, combination therapy, antibody-drug conjugates and radiotherapy. Furthermore, the combination of the PDX model with multiomics and single-cell analyses for cancer research has also been emphasized. The application of the PDX model in clinical treatment and personalized medicine is additionally emphasized.

For delivering high radiation doses to pancreatic tumors, organ motion management is indispensable; however, studies on this are limited. We aimed to evaluate the efficacy and safety of dynamic tumor tracking (DTT) moderately hypofractionated intensity-modulated radiotherapy (IMRT) in patients with locally advanced pancreatic cancer (LAPC).

Patients with histological confirmation for LAPC were included. A linac system, which was mounted with a gimbal function, was used for DTT-IMRT. The prescribed dose was 48 Gy in 15 fractions. The primary endpoint was the 1-year rate of freedom from locoregional progression (FFLP).

DTT-IMRT was successfully administered in 25 patients enrolled from four institutions. The median range of respiratory motion during DTT-IMRT was 9.8 mm (range: 3.5-27.3 mm), and the median tracking accuracy was 2.6 mm (range: 0.7-5.2 mm). With a median follow-up period of 13.9 months, the 1-year FFLP rate was 75.3% (lower limit of one-sided 80% confidence interval [CI]: 60.2%), which satisfied the predetermined primary endpoint. One-year locoregional progression-free survival, progression-free survival, and overall survival were 56.0% (95% CI: 34.8%-72.7%), 44.0% (95% CI: 24.5%-61.9%), and 60.0% (95% CI: 38.4%-76.1%), respectively. Regarding nonhematologic toxicities, grade 3 acute gastrointestinal (GI) toxicity was observed in two patients (8%), and two patients (8%) each experienced grade 3 late GI and non-GI toxicities. No grade 4 or 5 nonhematologic toxicities were observed.

DTT moderately hypofractionated IMRT shows preferable locoregional control without significant toxicity in patients with LAPC.

UMIN000017521.

Presence of active hepatitis C virus (HCV) infection may influence the outcome of patients treated for hepatocellular carcinoma (HCC), although this issue has never been adequately assessed in a large series of patients. The aim of this study was to evaluate whether the presence of active HCV affects the survival of patients treated for HCC.

This study assessed the outcome of 3123 anti-HCV-positive patients with HCC, subdivided according to the presence of active HCV infection or previous sustained virological response (SVR). Comparisons were also carried out after propensity score matching (PSM) considering demographic, clinical and oncological characteristics.

The median overall survival from HCC treatment was longer in patients with SVR than in those with active HCV infection both before (n = 2118: 61.0 months [95% confidence internal (CI): 56.5-65.5] vs. n = 1005: 51.0 months [95% CI: 43.4-58.6]; p = 0.003) and after PSM (n = 1285: 60.0 months [95% CI: 55.3-64.7] vs. n = 926: 54.0 months [95% CI: 46.7-61.3]; p = 0.030). Active HCV infection was associated with a greater risk of mortality (hazard ratio: 1.22-1.27, p = 0.001) independently of liver- and tumour-related variables, and modality of HCC treatment. Death due to liver failure was more common in patients with active HCV infection (24.5% vs. 17.1%; p = 0.001), while non-liver-related causes of death were more common in patients with SVR (25.0% vs. 17.0%; p = 0.001).

SVR is associated with a better outcome in patients undergoing HCC treatment, thus suggesting that these patients may benefit from antiviral therapy for HCV independently of cure of HCC.

Computed tomography (CT) is crucial in oncologic imaging for precise diagnosis and staging. Beam-hardening artifacts from contrast media in the superior vena cava can degrade image quality and obscure adjacent structures, complicating lymph node assessment. This study examines the use of virtual monoenergetic reconstruction with photon-counting detector CT (photon-counting CT) to mitigate these artifacts.

The retrospective study included 50 patients who underwent thoracoabdominal scans. Virtual monoenergetic reconstructions at nine keV levels (60 to 140 keV) were analyzed for Hounsfield Unit (HU) stability, image noise, and artifact index in various regions of interest (ROIs): mediastinal adipose tissue (ROI 1 to 3) and vascular stations (ROI 4 to 6) were compared with reference tissue (ROI 7 to 8). The diagnostic image quality of the keV levels was assessed using a 5-point Likert Scale.

Lower keV values (60 to 80) exhibited higher image noise and lower HU stability in mediastinal adipose tissue compared with higher energies, with optimal noise reduction observed at 130 keV (ROI 1 to 3). HU stability in vascular structures (ROI 4 to 6) significantly improved above 80 keV, with the best performance at 140 keV. Artifact levels decreased progressively from 60 to 140 keV. Visually, keV levels of 110 keV (96% Likert ≥4) and 120 keV (60% Likert 4) were rated most diagnostically valuable, consistent with technical findings.

Virtual monoenergetic reconstructions with photon-counting CT effectively reduce beam-hardening artifacts near the superior vena cava, enhancing the visualization of lymph nodes and adjacent structures. This technology advances oncologic imaging by improving diagnostic accuracy in areas previously affected by artifact-related image degradation.

Purpose: To evaluate the use of yttrium-90 (Y90) dosimetry in predicting treatment outcomes when used following transarterial radioembolization with SIR-Spheres® (Resin Y90) in patients with hepatic tumors. Materials and Methods: This single institution retrospective analysis included 100 patients with hepatocellular carcinoma, colorectal carcinoma or other liver metastases who underwent transarterial radioembolization with resin Y90 and had imaging follow-up within one year of treatment. Mean tumor dose and mean dose to nontumor was calculated using voxel-based dosimetry software. Descriptive statistics were reported and methods of analyses included simple and multivariable linear regression, contingency table analyses, Kaplan-Meier estimation, and Cox proportional hazards models. Results: Of 100 patients included, 65 demonstrated tumor shrinkage following transarterial radioembolization. Of these, 20 (30.8%) had hepatocellular carcinoma, 22 (33.8%) had colorectal carcinoma, and 23 (35.4%) had other types of metastases. There was an association between tumor shrinkage and mean tumor dose (p = 0.0285) and mean dose to nontumor (p = 0.0028) in hepatocellular carcinoma patients, but not colorectal carcinoma, or the other subgroup. For all 100 patients, time to death and mean tumor dose was associated only in the other subgroup (p = 0.0260), but not in the hepatocellular or colorectal carcinoma groups. Time to death and mean dose to nontumor was associated in hepatocellular carcinoma patients (p = 0.0421), but not the colorectal carcinoma or other subgroup. Conclusions: Voxel-based dosimetry assessment is a tool that may be utilized to assist in predicting treatment outcomes in responders to transarterial radioembolization.

Tumor mutation burden (TMB), defined as the number of somatic mutations of tumor DNA, is a well-recognized immunotherapy biomarker endorsed by regulatory agencies and pivotal in stratifying patients for clinical decision-making. However, measurement errors can compromise the accuracy of TMB assessments and the reliability of clinical outcomes, introducing bias into statistical inferences and adversely affecting TMB thresholds through cumulative and magnified effects. Given the unavoidable errors with current technologies, it is essential to adopt modeling methods to determine the optimal TMB-positive threshold. Therefore, we proposed a universal framework, TMBocelot, which accounts for pairwise measurement errors in clinical data to stabilize the determination of hierarchical thresholds. TMBocelot utilizes a Bayesian approach based on the stationarity principle of Markov chains to implement an enhanced error control mechanism, utilizing moderately informative priors. Simulations and retrospective data from 438 patients reveal that TMBocelot outperforms conventional methods in terms of accuracy, consistency of parameter estimations, and threshold determination. TMBocelot enables precise and reliable delineation of TMB-positive thresholds, facilitating the implementation of immunotherapy. The source code for TMBocelot is publicly available at https://github.com/YixuanWang1120/TMBocelot.

To compare 1D (linear) tumor volume calculations and classification systems with 3D-segmented volumetric analysis (SVA), focusing specifically on their effectiveness in the evaluation and management of NF2-associated vestibular schwannomas (VS). VS were clinically followed every 6 months with cranial, thin-sliced (< 3 mm) MRI. We retrospectively reviewed and used T1-weighted post-contrast enhanced (gadolinium) images for both SVA and linear measurements. 3D-SVA was performed manually or combined with semiautomated segmentation by using axial planes. The maximum linear dimensions (MLD) were determined in three dimensions (anteroposterior, transverse, and craniocaudal planes) using axial and coronal planes. The MLD was cubed (MLD3), and orthogonal analysis (OA) was derived to establish comparability with the SVA. The Hannover and Koos classification was used to depict the size ratio in each MRI and tumor. A linear regression model was performed to compare 1D/classification systems to SVA, and the percentage deviation change of MLD3 and OA to SVA was established using a one-way multivariate variance analysis. 2586 SVA and 10344 linear measurements were performed in a cohort of 149 NF2 patients and 292 associated VS. All measurement techniques (MLD3, OA, KOOS, and Hannover) significantly (and strongly, r2 > 0.5) correlated with SVA (p < 0.001). The OA showed an even stronger positive correlation than the MLD3 to SVA. Smaller classified tumors (T1/T2, K1/K2) exhibited a low-moderate positive correlation (r2 = 0.23-0.44) compared to medium-sized (T3, K2/3) and large tumors (T4, K4; r2 = 0.54-0.76). Pre- and postoperative MLD3 and OA statistically significantly predict SVA (p < 0.001), but the postoperative correlation was weaker, particularly for MLD3 to SVA values. All analyses showed a large scatter range. In the percentage deviation analysis of MLD3 and OA from SVA, small tumors (K1/K2, T1/T2) were overestimated. Compared to the SVA, the MLD3 and especially the OA are a time-saving alternative for monitoring the tumor volume of NF2-associated VS. However, the scatter range in small/surgically reduced tumors is enormous. For this reason, they are not recommended for monitoring off-label therapy with Bevacizumab or for treatment decisions depending on a precise assessment of tumor volume and growth. Developing deep learning-based volume determinations in the future is essential to reduce SVA's time intensity.

Patients with peritoneal metastasis from gastric cancer show poor prognosis with standard systemic chemotherapy. This prospective multicenter phase II clinical trial was performed to evaluate the efficacy and safety of intraperitoneal paclitaxel combined with systemic S-1 plus oxaliplatin for patients with advanced or recurrent gastric cancer with peritoneal metastasis.

Patients with advanced or recurrent gastric cancer with histologically or radiologically confirmed peritoneal metastases were eligible for the study. The chemotherapy regimen consisted of eight cycles of intraperitoneal paclitaxel 80 mg/m2 on days 1 and 8, combined with 80 mg/m2 S-1 for days 1-14, and 100 mg/m2 oxaliplatin on day 1, repeated every 21 days. The primary endpoint was 6-month progression-free survival. One-year progression-free and overall survival, response rate, and safety were set as the secondary endpoints.

In total, 28 patients were included in the study, of which 24 were analyzed, with the exception of those lost to follow-up and withdrawal of consent. The 6-months progression-free survival was 82.6 % (95 % CI: 68.5-99.6 %). The one-year progression-free and overall survival rates were 69.6 % (95 % CI: 53.1-91.2 %) and 76.9 % (95 % CI: 61-97 %), respectively. The overall response rate was 41.67 %. The hematologic toxicity profile showed grade 3/4 hematologic toxicities such as leukopenia (20.8 %), neutropenia (41.7 %), and thrombocytopenia (8.3 %). The only non-hematologic adverse event was grade 3 diarrhea. Three (12.5 %) patients experienced intraperitoneal chemoport-related adverse events.

Bidirectional intraperitoneal paclitaxel with systemic S-1 plus oxaliplatin shows promising efficacy and safety in the treatment of peritoneal metastatic gastric cancer.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and young adults. Typically, treatment involves a multimodal approach, with radiotherapy (RT) being a standard choice alongside surgical resection for local control, particularly in cases harboring fusions involving FOXO1. However, the long-term consequences of offering RT especially to the extremity in children can be significant including growth delay, contracture, arthritis, and secondary malignancy. Herein, we report the outcome of 10 consecutive patients with extremity RMS from two high-volume institutions who did not receive RT to primary site.

Demographic, genetic, tumor characteristics, surgical details, post-resection overall survival and event-free survival data were retrospectively collected from the CanSaRCC (Canadian Sarcoma Research and Clinical Collaboration) database.

Despite the absence of adjuvant RT to the primary tumor site, 90 % of this cohort patients experienced no local failure and the single patient with local failure was subsequently salvaged with RT and further chemotherapy.

By presenting this distinctive real-world data, our aim is to illustrate that in a select high-volume pediatric sarcoma center, extremity RMS can potentially be effectively managed through surgery and chemotherapy alone.

Clinical research paper.

Level IV.

Transcatheter arterial chemoembolization (TACE) is a proven and widely accepted treatment option for hepatocellular carcinoma and it is recommended as first-line non-curative therapy for BCLC B/intermediate HCC (preserved liver function, multifocal, no cancer-related symptoms) in patients without vascular involvement. Different types of TACE are available nowadays, including TAE, c-TACE, DEB-TACE, and DSM-TACE, but at present there is insufficient evidence to recommend one TACE technique over another and the choice is left to the operator. This review then aims to provide a comprehensive overview of the current literature on indications, types of procedures, safety, and efficacy of different TACE treatments.

To assess agreement between CT volumetry change classifications derived from Quantitative Imaging Biomarker Alliance Profile cut-points (ie, QIBA CTvol classifications) and the Response Evaluation Criteria in Solid Tumors (RECIST) categories.

Target lesions in lung, liver, and lymph nodes were randomly chosen from patients in 10 historical clinical trials for various cancers, ensuring a balanced representation of lesion types, diameter ranges described in the QIBA Profile, and variations in change magnitudes. Three radiologists independently segmented these lesions at baseline and follow-up scans using 2 software tools. Two types of predefined disagreements were assessed: Type I: substantive disagreement, where the disagreement between QIBA CTvol classifications and RECIST categories could not be attributed to the improved sensitivity of volumetry in detecting changes; and Type II: disagreement potentially arising from the improved sensitivity of volumetry in detecting changes. The proportion of lesions with disagreements between QIBA CTvol and RECIST, as well as the type of disagreements, was reported along with 95% CIs, both overall and within subgroups representing various factors.

A total of 2390 measurements from 478 lesions (158 lungs, 170 livers, 150 lymph nodes) in 281 patients were included. QIBA CTvol agreed with RECIST in 66.6% of interpretations. Of the 33.4% of interpretations with discrepancies, substantive disagreement (Type I) occurred in only 1.5% (95% CI: [0.8%, 2.1%]). Factors such as scanner vendor (P = .584), segmentation tool (P = .331), and lesion type (P = .492) were not significant predictors of disagreement. Significantly more disagreements were observed for larger lesions (≥50 mm, as defined in the QIBA Profile).

We conclude that QIBA CTvol classifications agree with RECIST categories.

Synchronous liver metastases occur in approximately 15-20% of patients with colorectal cancer. Optimal oncological treatment of oligometastatic disease combines surgical resection and systemic therapy. Open simultaneous resection of the primary and liver metastases is well described, but there is not much evidence for the increasing use of the minimally invasive approach. We here report the results of our experience of simultaneous minimally invasive resections.

A prospective database of patients with resection of colorectal liver metastases (CRLM) at the Charité - Universitätsmedizin Berlin was used for retrospective data analysis. We report all patients undergoing simultaneous minimal invasive resection of colorectal cancer and its synchronous liver metastases between May 2015 and December 2021.

Out of 281 patients undergoing resection of CRLM, 33 (11.7%) patients had simultaneous minimal invasive resection of the colorectal primary. The primary tumor was located mostly within the rectum (n = 17; 48.6%), followed by the descending colon (n = 6; 17.1%). CRLM were localized in both liver lobes in 69.7% (n = 23) of cases. Following resection of the colorectal tumor, an anastomosis was performed in 31 of 33 patients (93.9%), with no anastomotic leakage observed in the follow up. Simultaneous liver resections were performed mostly as subsegment (n = 20) or bisegment resections (n = 11). Mean IWATE-Score of all hepatic resections was 5.5 (± 2.4). Complication rates (Clavien-Dindo ≥ 3) were similar compared between low/intermediate and advanced/expert difficulty for liver resection (n = 4, 17.4% vs. n = 2, 20.0%; p = 1.0). In one case conversion to open resection was required.

Our data indicate that simultaneous minimal invasive resection of CRLM and the primary tumor is a safe and feasible procedure. Complication rates were consistent across different levels of difficulty (low to expert) in liver resections. Therefore, indications for simultaneous resection may be expanded.

A plant-based diet is associated with better survival among patients with nonmetastatic colorectal cancer (CRC), but its association in metastatic CRC is unknown.

Using an National Cancer Institute-sponsored trial (CALGB/SWOG 80405), we included 1284 patients who completed validated food frequency questionnaires at the initiation of metastatic CRC treatment. We calculated 3 indices: overall plant-based diet index (PDI), which emphasized consumption of all plant foods while reducing animal food intake; healthful plant-based diet index (hPDI), which emphasized consumption of healthful plant foods such as whole grains, fruits, and vegetables; and unhealthful plant-based diet index (uPDI), which emphasized consumption of less healthful plant foods such as fruit juices, refined grains, and sugar-sweetened beverages. We estimated the associations of 3 indices (quintiles) with overall survival (OS) and progression-free survival (PFS) using multivariable Cox proportional hazards regression.

We observed 1100 deaths and 1204 progression events (median follow-up = 6.1 years). Compared with the lowest quintile, patients in the highest quintile of PDI had significantly better survival (hazard ratio [HR] for OS = 0.76 [0.62-0.94], Ptrend = .004; PFS = 0.81 [0.66-0.99], Ptrend = .09). Similar findings were observed for hPDI (HR for OS = 0.81 [0.65-1.01], Ptrend = .053; PFS = 0.80 [0.65-0.98], Ptrend = .04), whereas uPDI was not associated with worse survival (HR for OS = 1.16 [0.94-1.43], Ptrend = .21; PFS = 1.12 [0.92-1.36], Ptrend = .42).

Our study suggests that a plant-based diet, especially when rich in healthful plant foods, is associated with better survival among patients with metastatic CRC. The cause of survival benefits warrants further investigation.

Hepatectomy is the optimal treatment for less than 20 % patients with hepatocellular carcinoma (HCC). A combination of hepatic artery infusion chemotherapy and systemic therapy-based conversion therapy provides a chance of resection for those with unresectable HCC. Yet, the prognosis for those successfully conversion resection is still unknown. The study is to determine the factors predicted prognosis of patients after conversion hepatic resection.

A total of 343 HCC patients underwent hepatectomy following conversion therapy from August 2018 to April 2023. Univariate and multivariate analysis were used to screen for independent factors affecting patients' prognosis.

One hundred and fifty-seven (45.8 %) patients developed recurrence or metastasis at a median time of 16.7 months (95 % CI 12.4-21.0 months) from hepatectomy. Univariate and multivariate analysis identified tumor number, alpha fetoprotein (AFP) response, tumor response, and successful downstaging were independent recurrent-free survival related predictors. Albumin bilirubin (ALBI) score and AFP response were independent death related predictors.

Clinical parameters reflecting the depth of conversion therapy response, were promising in predicting prognosis for HCC patients after conversion hepatic resection.

The prognosis of advanced gastric cancer (GC) with extensive lymph node (LN) metastasis treated with surgery alone remains poor. We conducted a multicenter phase II study to evaluate the efficacy and safety of perioperative capecitabine plus oxaliplatin (CapeOx) therapy in patients with advanced GC with extensive LN metastases.

Patients with histologically proven HER2-negative or unknown gastric adenocarcinoma with paraaortic LN (PALN) metastases and/or bulky LN metastases located at the celiac axis, common hepatic artery, and/or splenic artery were included in the study. Patients received three cycles of preoperative CapeOx every 3 weeks, followed by five cycles of postoperative CapeOx after gastrectomy with D2 or D2 + including PALN dissection. The primary endpoint was the response rate (RR) according to the RECIST v1.0 criteria.

Thirty patients from 14 institutions were enrolled from September 2017 to June 2022. Complete response, partial response, stable disease, and progressive disease occurred in zero, 20, eight, and one patient, respectively. One patient was not evaluated. The RR was 66.7% (90% confidence interval, 50.1-80.7%; one-sided P = 0.049). The preoperative chemotherapy completion rate and the curative resection rate were 96.7% and 93.3%, respectively. The minor (grade ≥ 1b) pathological RR was 66.7%. Grade 3 adverse events of preoperative chemotherapy included neutropenia in 3.3%, anemia in 6.7%, and anorexia in 10.0%. One treatment-related death occurred due to postoperative complications.

Preoperative CapeOx chemotherapy showed a favorable RR, curative resection rate, and acceptable adverse events in patients with advanced GC with extensive LN metastasis.

UMIN000028749 and jRCTs051180186.

This study aimed to determine the maximum tolerated dose (MTD) of the urokinase plasminogen activator (uPA) inhibitor upamostat (LH011) in combination with gemcitabine for locally advanced unresectable or metastatic pancreatic cancer.

Seventeen patients were enrolled and received escalating doses of oral LH011 (100, 200, 400, or 600 mg) daily alongside 1000 mg/m2 of gemcitabine. Safety profiles, tumor response (including response rate and progression-free survival), pharmacokinetics, and changes in CA199 and D-dimer levels were assessed.

During the study period (Day0-Day49), no patients achieved partial response. Stable disease (SD) was observed in 12 patients (70.6%), while four patients (23.5%) experienced progressive disease (PD). One patient withdrew due to a serious adverse event (SAE) on D47. Pharmacokinetic analysis revealed a dose-related increase in LH011 and its metabolite WX-UK1 exposure from 100 to 400 mg but not in the 600 mg group. Hematological toxicity, mainly attributable to gemcitabine, was the predominant grade 3 or 4 adverse event, with additional occurrences of loss of appetite, rash, and interstitial lung disease. Sinus bradycardia possibly linked to LH011 rather than gemcitabine was noted. The MTD was not reached.

Combining LH011 at doses ranging from 100 to 600 mg with gemcitabine every 21 days demonstrated manageable safety and tolerability. However, tumor response did not significantly differ among the dose groups, suggesting the need for further investigation.

NCT05329597.

Over the past two decades, the globalization of oncology clinical trials has expanded, yet significant disparities persist across countries. This study aimed to evaluate these geographical inequalities, the evolution of trial phases, and the adherence to ethical standards according to the World Bank's income group.

The ClinicalTrials.gov database was searched and recorded in June 2024. We analyzed data from 87 748 oncology clinical trials conducted between 2000 and 2021, across high-income (HICs), upper-middle-income (UMICs), lower-middle-income (LMICs), and low-income countries. Key metrics included trial density, funding sources, registration timing, and trial phase distribution.

The number of oncology trials increased significantly, with a mean absolute annual rise of 266.6 trials, with China currently being the leading site of early- and validation-phase trials. While HICs still present the highest trial densities, UMICs showed a notable increase in early-phase trials, reflecting a shift in research dynamics. However, despite these advances, 76.4% of countries still had no new trials initiated by 2024. Additionally, ethical practices saw improvement from 2005 to 2021 with an increase in pre-commencement registration (from 9.2% to 58%, P < 0.0001), and more validation-phase trials with a survival variable as the primary outcome (from 40% to 59.6%, P < 0.0001).

Despite the growth in oncology clinical trials, significant disparities in trial distribution and access remain, especially in LMICs. Continued investments in research infrastructure and adherence to ethical standards are crucial to ensure that clinical research benefits are equitably distributed, particularly in regions with the greatest need for advanced cancer therapies.

Colorectal cancer (CRC) is one of the most frequent malignancies and, despite screening programs, it is often diagnosed at late stages. Although current first- and second-line therapies stratify for KRAS/NRAS/BRAF mutations, microsatellite instability, tumour location and co-morbidities, the therapeutic mainstay for the first- and second-line treatment of the majority of patients consists of 5-fluorouracil (5-FU)-based chemo-immunotherapy. The present study evaluated the responses of patients with stage IV CRC, treated at the University Hospital Krems between January 1, 2015 and December 31, 2021, who received at least two therapy lines (n=49), with the aim of investigating whether the response to first-line therapy could predict the response to second-line therapy. All patients with first-line complete response (CR) had at least stable disease in response to second-line treatment [overall response rate (ORR)=66.6%]. On the other hand, all patients with progressive disease (PD) in response to first-line treatment (n=7) did not respond to second-line therapy (ORR=0%). These findings also translated to overall survival (OS): Patients with first-line CR had a median OS time of 80 months, whereas patients with PD had a median OS time of 12 months (P<0.001). Furthermore, different parameters were analysed for their impact on OS; the results revealed that BRAF alterations were associated with poor prognosis. Other factors (sex, tumor sidedness, KRAS and MSS/MSI status) had in this cohort no significant effect on OS. In conclusion, the present study demonstrated that, with current treatment strategies applying 5-FU-based chemo-immunotherapy as first- and second-line treatment for patients with metastatic CRC, response to first-line therapy may be a strong predictor for the response to second-line therapy and OS. By exchanging the chemotherapeutic combination partner from oxaliplatin to irinotecan or vice versa, plus the additive anti-epidermal growth factor receptor/anti-vascular endothelial growth factor antibody, the negative factor of non-response to first-line therapy could not be overcome by second-line treatment in this study population. These findings must be confirmed in larger studies, but indicate the need for novel treatment options, especially for patients not responding to first-line 5-FU-based chemo-immunotherapy.