BACKGROUND: Systemic inflammatory response (SIR) indicators are an emerging category of serum biomarkers with significant potential as prognostic and predictive factors in various types of cancers The primary focus of our study was to determine the prognostic value of the lymphocyte-to-monocyte ratio (LMR), platelet-to-albumin ratio (PLR) and platelet-to-albumin ratio (PAR) in evaluating the response to neoadjuvant treatment for patients with rectal cancer.
METHODS: We included 99 consecutive patients with rectal cancer which were admitted for surgery in our institution after completing a standard neoadjuvant radio-chemotherapy regimen. Several hematologic parameters, including LMR, PAR and PLR, were calculated by collecting and analyzing blood samples preoperatively. Cases were divided into groups using ROC curve analysis to determine optimal cutoff values for each of the investigated parameters. Treatment response was assessed through histopathological analysis of the resected specimens.
RESULTS: PLR values over 215.2 were correlated with the presence of lymph node metastasis. A similar correlation was observed between PAR values over 41.89 and lymph node positivity. A significant correlation was observed between the presence of tumor budding on histopathological analysis and high-PAR values. A statistically significant correlation between a high PLR and a good response to neoadjuvant treatment was determined.
CONCLUSIONS: High PLR values may be associated with a more favorable treatment response to neoadjuvant radio-chemotherapy. A high PAR may be associated with unfavorable histopathological characteristics. Further studies on these readily available biomarkers are required in order to validate their clinical utility.

Purpose: Clinical evidence suggests an association between comorbidities and outcome in patients with glioblastoma (GBM). We hypothesised that the internal carotid artery (ICA) calcium score could represent a promising prognostic biomarker in a competing risk analysis in patients diagnosed with GBM. Methods: We validated the use of the ICA calcium score as a surrogate marker of the coronary calcium score in 32 patients with lung cancer. Subsequently, we assessed the impact of the ICA calcium score on overall survival in GBM patients treated with radio-chemotherapy. Results: We analysed 50 GBM patients. At the univariate analysis, methyl-guanine-methyltransferase gene (MGMT) promoter methylation (p = 0.048), gross total tumour resection (p = 0.017), and calcium score (p = 0.011) were significant prognostic predictors in patients with GBM. These three variables also maintained statistical significance in the multivariate analysis. Conclusions: the ICA calcium score could be a promising prognostic biomarker in GBM patients.

BACKGROUND: The PACIFIC study showed that after radio-chemotherapy, patients with NSCLC derived a benefit in PFS and OS when treated with durvalumab. This effect was limited to patients with a PD-L1 expression of >1%, partly because the outcome in the observational control arm was surprisingly favorable. Thus, it could be speculated that a lack of PD-L1 expression confers a favorable outcome for patients with stage III NSCLC.
METHODS: Clinical data, PD-L1 expression, predictive blood markers, and the outcomes of 99 homogeneously treated patients with stage III NSCLC were retrospectively captured. Statistical analyses using the log rank test were performed.
RESULTS: The median OS of patients with an expression of PD-L1 < 1% was 20 months (CI 10.5-29.5) and the median OS of patients with an expression of PD-L1 ≥ 1% was 28 months (CI 16.5-39.2) (p = 0.734). The median PFS of patients with an expression of PD-L1 < 1% was 9 months (CI 6.3-11.6) and the median PFS of patients with an expression of PD-L1 ≥ 1% was 12 months (CI 9.8-14.2) (p = 0.112).
CONCLUSIONS: The assumption that the lack of PD-L1 expression represents a favorable prognostic factor after radio-chemotherapy vs. PD-L1 expression > 1% was not confirmed.

The treatment of superficial rectal cancers (local excision, or proctectomy with total mesorectal excision (TME) remains controversial. Endoscopy and endorectal ultrasonography are essential for the precise initial definition of these small cancers. During endoscopy, the depth of the lesion can be estimated using virtual chromoendoscopy with magnification, thereby aiding the assessment of the possibilities of local excision. Current international recommendations indicate completion proctectomy after wide local excision for cases where the pathologic examination reveals poorly-differentiated lesions, lymphovascular invasion, grade 2 or 3 tumor budding, and incomplete resection. But debate persists regarding whether the depth of submucosal invasion can accurately predict the risk of lymph node spread. Recent data from the literature suggest that the depth of submucosal invasion should no longer, by itself, be an indication for additional oncological surgery. Adjuvant radio-chemotherapy could be an alternative to completion proctectomy in patients with pT1 rectal cancer and unfavorable histopathological criteria. A Dutch randomized controlled trial is underway to validate this strategy.

Oncologists and applied mathematicians are interested in understanding the dynamics of cancer-immune interactions, mainly due to the unpredictable nature of tumour cell proliferation. In this regard, mathematical modelling offers a promising approach to comprehend this potentially harmful aspect of cancer biology. This paper presents a novel dynamical model that incorporates the interactions between tumour cells, healthy tissue cells, and immune-stimulated cells when subjected to simultaneous chemotherapy and radiotherapy for treatment. We analysed the equilibria and investigated their local stability behaviour. We also study transcritical, saddle-node, and Hopf bifurcations analytically and numerically. We derive the stability and direction conditions for periodic solutions. We identify conditions that lead to chaotic dynamics and rigorously demonstrate the existence of chaos. Furthermore, we formulated an optimal control problem that describes the dynamics of tumour-immune interactions, considering treatments such as radiotherapy and chemotherapy as control parameters. Our goal is to utilize optimal control theory to reduce the cost of radiotherapy and chemotherapy, minimize the harmful effects of medications on the body, and mitigate the burden of cancer cells by maintaining a sufficient population of healthy cells. Cost-effectiveness analysis is employed to identify the most economical strategy for reducing the disease burden. Additionally, we conduct a Latin hypercube sampling-based uncertainty analysis to observe the impact of parameter uncertainties on tumour growth, followed by a sensitivity analysis. Numerical simulations are presented to elucidate how dynamic behaviour of model is influenced by changes in system parameters. The numerical results validate the analytical findings and illustrate that a multi-therapeutic treatment plan can effectively reduce tumour burden within a given time frame of therapeutic intervention.

Metal-based drugs currently dominate the field of chemotherapeutic agents; however, achieving the controlled activation of metal prodrugs remains a substantial challenge. Here, we propose a universal strategy for the radiation-triggered activation of metal prodrugs via nanosurface energy transfer (NSET). The core-shell nanoplatform (Ru-GNC) is composed of gold nanoclusters (GNC) and ruthenium (Ru)-containing organic-inorganic hybrid coatings. Upon X-ray irradiation, chemotherapeutic Ru (II) complexes were released in a controlled manner through a unique NSET process involving the transfer of photoelectron energy from the radiation-excited Ru-GNCs to the Ru-containing hybrid layer. In contrast to the traditional radiation-triggered activation of prodrugs, such an NSET-based system ensures that the reactive species in the tumor microenvironment are present in sufficient quantity and are not easily quenched. Additionally, ultrasmall Ru-GNCs preferably target mitochondria and profoundly disrupt the respiratory chain upon irradiation, leading to radiosensitization by generating abundant reactive oxygen species. Consequently, Ru-GNC-directed radiochemotherapy induces immunogenic cell death, resulting in significant therapeutic outcomes when combined with the programmed cell death-ligand 1 (PD-L1) checkpoint blockade. This NSET strategy represents a breakthrough in designing radiation-triggered nanoplatforms for metal-prodrug-mediated cancer treatment in an efficient and controllable manner.

Immunotherapy is actively explored in glioblastoma (GBM) to improve patient prognosis. Tumor-associated macrophages (TAMs) are abundant in GBM and harnessing their function for anti-tumor immunity is of interest. They are plastic cells that are influenced by the tumor microenvironment, by radio-chemotherapy and by their own phagocytic activity. Indeed, the engulfment of necrotic cells promotes pro-inflammatory (and anti-tumoral) functions while the engulfment of apoptotic cells promotes anti-inflammatory (and pro-tumoral) functions through efferocytosis.
To model the effect of radio-chemotherapy on the GBM microenvironment, we exposed human macrophages to supernatant of treated GBM cells in vitro. Macrophages were derived from human monocytes and GBM cells from patient-resected tumors. GBM cells were exposed to therapeutically relevant doses of irradiation and chemotherapy. Apoptosis and phagocytic activity were assessed by flow cytometry.
The phagocytic activity of macrophages was increased, and it was correlated with the proportion of apoptotic GBM cells producing the supernatant. Whether uptake of apoptotic tumor cells could occur would depend upon the expression of efferocytosis-associated receptors. Indeed, we showed that efferocytosis-associated receptors, such as AXL, were upregulated.
We showed that macrophage phagocytic activity increased when exposed to supernatant from GBM cells treated by radio-chemotherapy. However, as efferocytosis-associated receptors were up-regulated, this effect could be deleterious for the anti-GBM immune response. We speculate that by inducing GBM cell apoptosis in parallel to an increase in efferocytosis receptor expression, the impact of radio-chemotherapy on phagocytic activity could promote anti-inflammatory and pro-tumoral TAM functions.

Anaplastic thyroid carcinoma is a rare and aggressive form of thyroid cancer that has a poor prognosis and a high mortality rate. It is characterized by rapid growth and invasion of nearby tissues. It typically presents as a rapidly growing goiter or nodule that is firm to the touch and firmly attached to the underlying structures. Case reports of unusual presentations of anaplastic thyroid carcinoma have been reported. The presentation of anaplastic thyroid carcinoma mimicking cervical tuberculosis is very unusual. We reported a case of a 65-year-old patient who had a left cervical swelling that had been evolving for 4 months, causing dysphagia. Initial imaging showed a necrotic mass in the left lobe of the thyroid, communicating with a second necrotic mass in the subcutaneous tissue that was fistulized to the skin and suggesting cervical tuberculosis. The mass was incised with pus and whitish material resembling caseous tuberculosis was discharged. Acid-fast bacilli (AFB) Polymerase chain reaction (PCR) was negative and biopsy revealed a nonspecific granulomatous lesion. Due to the growth of the mass and the presence of a permeation nodule, a second biopsy was performed, revealing anaplastic thyroid carcinoma. The patient was referred for radiochemotherapy due to tumor inoperability.

BACKGROUND: A significant number of clinical trials must be prematurely discontinued due to recruitment failure, and only a small fraction publish results and a failure analysis. Based on our experience on conducting the NEOPA trial on neoadjuvant radiochemotherapy for resectable and borderline resectable pancreatic carcinoma (NCT01900327-funded by the German Federal Ministry of Education and Research-BMBF), we performed an analysis of potential reasons for recruitment failure and general problems in conducting clinical trials in Germany.
METHODS: Systematic analysis of environmental factors, trial history, conducting and funding in the background of the published literature.
RESULTS: The recruitment failure was based on various study-specific conceptional and local environmental aspects and in peculiarities of the German surgical study culture. General reservations against a neo-adjuvant study concept combined with game changing scientific progresses during the long-lasting planning and funding phase have led to a reduced interest in the trial design and recruitment.
CONCLUSIONS: Trial planning and conducting should be focused, professionalized and financed on a national basis. Individual interests must be subordinated to reach the goal to perform more relevant and successful clinical trials in Germany. Bureaucratic processes must be further fastened between a trial idea and the start of a study.

BACKGROUND: Unplanned early readmission (UER) within 30 days after hospital release is a negative prognostic marker for patients diagnosed with glioblastoma (GBM). This work analyzes the impact of UER on the effects of standard therapy modalities for GBM patients, including the extent of resection (EOR) and adjuvant therapy regimen.
METHODS: Records were searched for patients with newly diagnosed GBM between 2014 and 2020 who were treated at our facility. Exclusion criteria were being aged below 18 years or missing data. An overall survival (OS) analysis (Kaplan-Meier estimate; Cox regression) was performed on various GBM patient sub-cohorts.
RESULTS: A total of 276 patients were included in the study. UER occurred in 13.4% (n = 37) of all cases, significantly reduced median OS (5.7 vs. 14.5 months, p < 0.001 by logrank), and was associated with an increased hazard of mortality (hazard ratio 3.875, p < 0.001) in multivariate Cox regression when other clinical parameters were applied as confounders. The Kaplan-Meier analysis also showed that patients experiencing UER still benefitted from adjuvant radio-chemotherapy when compared to radiotherapy or no adjuvant therapy (p < 0.001 by logrank). A higher EOR did not improve OS in GBM patients with UER (p = 0.659).
CONCLUSIONS: UER is negatively associated with survival in GBM patients. In contrast to EOR, adjuvant radio-chemotherapy was beneficial, even after UER.