The advancement of novel technologies, coupled with bioinformatics, has led to the discovery of additional genes, such as long noncoding RNAs (lncRNAs), that are associated with drug resistance. LncRNAs are composed of over 200 nucleotides and do not possess any protein coding function. These lncRNAs exhibit lower conservation across species, are typically expressed at low levels, and often display high specificity towards specific tissues and developmental stages. The LncRNA MALAT1 plays crucial regulatory roles in various aspects of genome function, encompassing gene transcription, splicing, and epigenetics. Additionally, it is involved in biological processes related to the cell cycle, cell differentiation, development, and pluripotency. Recently, MALAT1 has emerged as a novel mechanism contributing to drug resistance or sensitivity, attracting significant attention in the field of cancer research. This review aims to explore the mechanisms through which MALAT1 confers resistance to chemotherapy and radiotherapy in cancer cells.

Lung cancer remains the most common cause of cancer death across the world. Non-small-cell lung cancer (NSCLC) represents the most frequent type of lung cancer and is frequently diagnosed at an advanced stage. Stage III NSCLC, which encompasses 30% of cases, refers to a state between localized and metastatic disease, and is associated with poor prognosis. As highlighted in this review, stage III represents a heterogenous group, whose complex management includes multimodal treatment, discussed below, and requires discussion in multidisciplinary teams. The goal of this approach is a maximalist attitude in these patients with locally advanced and non-metastatic disease. However, many issues remain under debate including the optimal sequences of treatment between different treatment modalities, patient selection particularly for surgery, the duration of perioperative treatments and the identification of biomarkers to determine which patients might benefit of specific treatment like immunotherapy and targeted therapies. This review describes the current landscape of management of stage III NSCLC, discussing the critical issue of resectability, and highlighting the recent advancements in the field, particularly the incorporation of immune-checkpoint inhibitors (ICIs) and targeted therapies in this setting.

OBJECTIVE: Reliable and accessible biomarkers for patients with Head and Neck Squamous Cell Carcinoma (HNSCC) are warranted for biologically driven radiotherapy (RT). This study aimed to investigate the prognostic value of putative cancer stem cell (CSC) markers, hypoxia, and tumor volume using loco-regional high-dose failure (HDF) as endpoint.
METHODS: Tumor tissue was retrieved from patients treated with primary chemo-(C-)RT and nimorazole for HNSCC in the Danish Head and Neck Cancer Study Group (DAHANCA) 19 study. Tumor volume, hypoxic classification, and expression of CSC markers CD44, SLC3A2, and MET were analyzed. For patients with eligible data on all parameters (n = 340), the risk of HDF following primary chemo-(C-)RT were analyzed by these biomarkers as a whole and stratified for p16-positive oropharynx (p16 + OPSCC) vs p16-negative (p16-) tumors (oral cavity, p16- oropharynx, hypopharynx and larynx).
RESULTS: Higher risk of HDF was seen for patients with larger primary and nodal volume (>25 cm3, Hazard Ratio (HR): 3.00 [95 % CI: 1.73-5.18]), high SLC3A2 (HR: 2.99 [1.28-6.99]), CD44 (>30 % positive, HR: 2.29 [1.05-5.00]), and p16- tumors (HR: 2.53 [1.05-6.11]). p16- tumors had a higher CSC marker expression than p16 + OPSCC. The factors associated with the highest risk of HDF were larger volume (HR: 3.29 [1.79-6.04]) for p16- tumors (n = 178) and high SLC3A2 (HR: 6.19 [1.58-24.23]) for p16 + OPSCC (n = 162).
CONCLUSIONS: Tumor volume, p16, and CSC markers are potential biomarkers for HDF for patients with HNSCC treated with (C-)RT. Lower expression of CSC in p16 + OPSCC may contribute to better tumor control.

We focused on Differentiated pseudoprogression (PPN) of progression (PN) and the response to radiotherapy (RT) or chemoradiotherapy (CRT) using diffusion and metabolic imaging.
Seventy-five patients with glioma were included in this prospective study (approved by the Iranian Registry of Clinical Trials (IRCT) (IRCT20230904059352N1) in September 2023). Contrast-enhanced lesion volume (CELV), non-enhanced lesion volume (NELV), necrotic tumor volume (NTV), and quantitative values ​​of apparent diffusion coefficient (ADC) and magnetic resonance spectroscopy (Cho/Cr, Cho/NAA and NAA/Cr) were calculated by a neuroradiologist using a semi-automatic method. All patients were followed at one and six months after CRT.
The results of the study showed statistically significant changes before and six months after RT-CRT for M-CELV in all glioma types (𝑝 < 0.05). In glioma cell types, the changes in M-ADC, M-Cho/Cr, and Cho/NAA indices for PN were incremental and greater for PPN patients. M-NAA/Cr ratio decreased after six months which was significant only on PN for GBM, and Epn (𝑝 < 0.05). A significant difference was observed between diffusion indices, metabolic ratios, and CELV changes after six months in all types (𝑝 < 0.05). None of the patients were suspected PPN one month after treatment. The DWI/ADC indices had higher sensitivity and specificity (98.25% and 96.57%, respectively).
The results of the present study showed that ADC values and Cho/Cr and Cho/NAA ratios can be used to differentiate between patients with PPN and PN, although ADC is more sensitive and specific.

BACKGROUND: In case of locally advanced and/or non-metastatic unresectable esophageal cancer, definitive chemoradiotherapy (CRT) delivering 50 Gy in 25 daily fractions in combination with platinum-based regimen remains the standard of care resulting in a 2-year disease-free survival of 25% which deserves to be associated with new systemic strategies. In recent years, several immune checkpoint inhibitors (anti-PD1/anti-PD-L1, anti-Program-Death 1/anti-Program-Death ligand 1) have been approved for the treatment of various solid malignancies including metastatic esophageal cancer. As such, we hypothesized that the addition of an anti-PD-L1 to CRT would provide clinical benefit for patients with locally advanced oesophageal cancer. To assess the efficacy of the anti-PD-L1 durvalumab in combination with CRT and then as maintenance therapy we designed the randomized phase II ARION (Association of Radiochemotherapy with Immunotherapy in unresectable Oesophageal carciNoma- UCGI 33/PRODIGE 67).
METHODS: ARION is a multicenter, open-label, randomized, comparative phase II trial. Patients are randomly assigned in a 1:1 ratio in each arm with a stratification according to tumor stage, histology and centre. Experimental arm relies on CRT with 50 Gy in 25 daily fractions in combination with FOLFOX regimen administrated during and after radiotherapy every two weeks for a total of 6 cycles and durvalumab starting with CRT for a total of 12 infusions. Standard arm is CRT alone. Use of Intensity Modulated radiotherapy is mandatory. The primary endpoint is to increase progression-free survival at 12 months from 50 to 68% (HR = 0.55) (power 90%; one-sided alpha-risk, 10%). Progression will be defined with central external review of imaging.
UNASSIGNED: PD-L1 Combined Positivity Score on carcinoma cells and stromal immune cells of diagnostic biopsy specimen will be correlated to disease free survival. The study of gut microbiota will aim to determine if baseline intestinal bacteria correlates with tumor response. Proteomic analysis on blood samples will compare long-term responder after CRT with durvalumab to non-responder to identify biomarkers.
CONCLUSIONS: Results of the present study will be of great importance to evaluate the impact of immunotherapy in combination with CRT and decipher immune response in this unmet need clinical situation.
BACKGROUND: ClinicalTrials.gov, NCT: 03777813.Trial registration date: 5th December 2018.

BACKGROUND: Currently, radiation therapy treatment planning system intends biological optimization that relies heavily upon plan metrics from tumor control probability (TCP) and normal tissue complication probability (NTCP) modeling. Implementation and expansion of TCP and NTCP models with alternative data is an important step towards reliable radiobiological treatment planning. In this retrospective single institution study, the treatment charts of 139 lung cancer patients treated with chemo-radiotherapy were reviewed and correlated dosimetric predictors with the incidence of esophagitis and established NTCP model of esophagitis grade 1 and 2 for lung cancer patients.
METHODS: Esophagus is an organ at risk (OAR) in lung cancer radiotherapy (RT). Esophagitis is a common toxicity induced by RT. In this study, dose volume parameters Vx (Vx: percentage esophageal volume receiving ≥ x Gy) and mean esophagus dose (MED) as quantitative dose-volume metrics, the esophagitis grade 1 and 2 as endpoints, were reviewed and derived from the treatment planning system and the electronic medical record system. Statistical analysis of binary logistic regression and probit were performed to have correlated the probability of grade 1 and 2 esophagitis to MED and Vx. IBM SPSS software version 24 at 5% significant level (α = 0.05) was used in the statistical analysis.
RESULTS: The probabilities of incidence of grade 1 and 2 esophagitis proportionally increased with increasing the values of Vx and MED. V20, V30, V40, V50 and MED are statistically significant good dosimetric predictors of esophagitis grade 1. 50% incidence probability (TD50) of MED for grade 1 and 2 esophagitis were determined. Lyman Kutcher Burman model parameters, such as, n, m and TD50, were fitted and compared with other published findings. Furthermore, the sigmoid shaped dose responding curve between probability of esophagitis grade 1 and MED were generated respecting to races, gender, age and smoking status.
CONCLUSIONS: V20, V30, V40 and V50 were added onto Quantitative Analysis of Normal Tissue Effects in the clinic, or QUANTEC group\'s dose constrains of V35, V50, V70 and MED. Our findings may be useful as both validation of 3-Dimensional planning era models and also additional clinical guidelines in treatment planning and plan evaluation using radiobiology optimization.

A pivotal cause of death in the modern world, cancer is an insidious pathology that should be diagnosed at an early stage for successful treatment. Development of therapeutic interventions with minimal invasiveness and high efficacy that can discriminate between tumor and normal cells is of particular interest to the clinical science, as they can enhance patient survival. Nanoparticles are an invaluable asset that can be adopted for development of such diagnostic and therapeutic modalities, since they come in very small sizes with modifiable surface, are highly safe and stable, and can be synthesized in a controlled fashion. To date, different nanoparticles have been incorporated into numerous modalities such as tumor-targeted therapy, thermal therapy, chemotherapy, and radiotherapy. This review article seeks to deliver a brief account of recent advances in research and application of nanoparticles in hyperthermia-based cancer therapies. The most recent investigations are summarized to highlight the latest advances in the development of combined thermo-chemo-radiotherapy, along with the challenges associated with the application of nanoparticles in cancer therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

OBJECTIVE: We investigated the dynamics of eosinophil depletion during definitive concurrent chemo-radiotherapy (CCRT) and their association with the prognosis of stage Ⅱ-Ⅳa nasopharyngeal carcinoma (NPC) patients.
METHODS: Fuzzy C-means algorithm (FCMA) assessed longitudinal trends in circulating eosinophil counts (CECs) of 1225 patients throughout the period of radical radiotherapy. The prognostic impact on patients\' survival was evaluated with Kaplan-Meier analysis and Cox proportional risk model was used to determine the hazard ratio for adverse prognostic effects in grades of eosinophil depletion. The interactive effect of pre-treatment CECs and CCRT on outcomes was evaluated using HRs within the framework of Cox regression models.
RESULTS: Three grades of eosinophil depletion, as defined by the interaction between dynamic types of CECs in the period of treatment and the value of CECs at the termination of treatment, significantly stratified the poor prognosis in terms of progression-free survival (PFS), overall survival (OS), and distant metastasis-free survival (DMFS) [1.57-fold (P = 0.001), 1.69-fold (P = 0.007), and 1.51-fold (P = 0.019) for G1, 2.4-fold (P < 0.001), 2.76-fold (P < 0.001), and 2.31-fold (P < 0.001) for G2, as compared with G0]. Furthermore, high levels of pre-treatment CECs acted as the strongest protective factor against severe depletion grade (G0 vs. G2, HR = 0.20, P = 0.005; G1 vs. G2, HR = 0.14, P < 0.001). However, compared with radiotherapy alone, the benefit from CCRT was attenuated in patients with high pre-treatment CECs.
CONCLUSIONS: CECs reduction after treatment in patients with NPC may be helpful in the clinical setting to aid in assessing the prognosis for standard treatment of NPC.

BACKGROUND: This study aimed to evaluate the prognosis of concurrent chemo-radiotherapy (CCRT) versus sequential chemo-radiotherapy (SCRT) induction followed by surgical resection in patients with advanced thymic epithelial tumors (TETs).
METHODS: This retrospective study included patients with advanced TETs who underwent CCRT or SCRT induction followed by surgical resection at the Second General Hospital of Guangdong Province between January 2008 and December 2019. The primary outcomes were induction response rate and surgical complete resection rate. The secondary outcomes were surgery combined resection, post-induction T staging, postoperative TNM staging, postoperative pathological tumor regression grade, progression-free survival (PFS) and overall survival (OS), and adverse events (AEs).
RESULTS: A total of 31 patients were included, 15 of whom received CCRT and the other 16 SCRT. The induction response rates were 80.0 and 62.5%, respectively, the post-induction step-down rates were 46.7 and 31.3%, respectively, and the post-induction R0 resection rates were 80.0 and 68.8%, respectively, without significant differences between CCRT and SCRT groups (all P > 0.05). The 5-year OS rate was 64.2 and 51.6%, respectively, and PFS was 42.3 and 21.4%, respectively, without significant differences between CCRT and SCRT groups (both P > 0.05). AEs in the hematologic system were significantly higher with CCRT compared with SCRT (P = 0.009).
CONCLUSIONS: Patients with advanced TETs might have a good prognosis with both CCRT and SCRT induction therapy, while SCRT induction may result in a lower probability of AEs in the hematologic system.

BACKGROUND: This study aims to investigate the prognostic significance of the pre-treatment hemoglobin-red blood cell distribution width (RDW) ratio (HRR) in terms of overall survival (OS) and disease-free survival (DFS) in patients with locally advanced nasopharyngeal cancer (LANC) treated with chemoradiotherapy.
METHODS: Patients with LANC who attended the oncology clinic between October 2010 and June 2020 were retrospectively screened. HRR was calculated as hemoglobin (g/dL) divided by the RDW (%). Patients were assigned to either the low HRR group or the high HRR group.
RESULTS: A total of 102 patients were included in the study. The cut-off value for HRR was taken as 0.97. Between the low and high HRR groups, mean age, Eastern Cooperative Oncology Group (ECOG) performance score, gamma-glutamyl transferase (GGT), albumin and lactate dehydrogenase (LDH) levels, weight loss at diagnosis, and recurrence and metastasis rate were significantly different. In the low HRR group, OS and DFS were 44.4 (95% CI: 4.9-83.8) and 15.7 months (95% CI: 0.1-36.2), respectively, but could not be reached in the high HRR group (p<0.001). In the multivariate analysis, low HRR was shown to be an independent factor in terms of both OS (p=0.004, hazard ratio (HR)=3.07, 95% CI: 1.444-6.529) and DFS (p<0.001, HR=3.94, 95% CI: 1.883-8.244).
CONCLUSIONS: This is the first study showing that HRR is an independent prognostic marker for OS and DFS in patients with LANC treated with chemoradiotherapy. Thus, HRR can be used as an easily applicable, inexpensive marker in clinical practice in this patient group.