Search

Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is characterized by high rate of recurrence, resulting in a poor survival. Standard treatments are associated with significant toxicities that impact the patient’s quality of life, highlighting the urgent need for novel therapies to improve patient outcomes. On this regard, noble metal nanoparticles (NPs) are emerging as promising agents as both drug carriers and radiosensitizers. On the other hand, co-treatments based on NPs are still at the preclinical stage because of the associated metal-persistence.In this bioconvergence study, we introduce a novel strategy to exploit tumour chorioallantoic membrane models (CAMs) in radio-investigations within clinical equipment and evaluate the performance of non-persistent nanoarchitectures (NAs) in combination with radiotherapy with respect to the standard concurrent chemoradiotherapy for the treatment of HPV-negative HNSCCs. A comparable effect has been observed between the tested approaches, suggesting NAs as a potential platinum-free agent in concurrent chemoradiotherapy for HNSCCs. On a broader basis, our bioconvergence approach provides an advance for the translation of Pt-free radiosensitizer to the clinical practice, positively shifting the therapeutic vs. side effects equilibrium for the management of HNSCCs.

Abstract Oral malignancies continue to have severe morbidity with less than 50% long-term survival despite the advancement in the available therapies. There is a persisting demand for new approaches to establish more efficient strategies for their treatment. In this regard, the human topoisomerase II (topoII) enzyme is a validated chemotherapeutics target, as topoII regulates vital cellular processes such as DNA replication, transcription, recombination, and chromosome segregation in cells. TopoII inhibitors are currently used to treat some neoplasms such as breast and small cells lung carcinomas. Additionally, topoII inhibitors are under investigation for the treatment of other cancer types, including oral cancer. Here, we report the therapeutic effect of a tetrahydroquinazoline derivative (named ARN21934) that preferentially inhibits the alpha isoform of human topoII. The treatment efficacy of ARN21934 has been evaluated in 2D cell cultures, 3D in vitro systems, and in chick chorioallantoic membrane cancer models. Overall, this work paves the way for further preclinical developments of ARN21934 and possibly other topoII alpha inhibitors of this promising chemical class as a new chemotherapeutic approach for the treatment of oral neoplasms.

Abstract Background Circulating cell-free DNA (cfDNA, liquid biopsy) is a powerful tool to detect molecular alterations. However, depending on tumor characteristics, biology and anatomic localization, cfDNA detection and analysis may be challenging. Gliomas are enclosed into an anatomic sanctuary, which obstacles the release of cfDNA into the peripheral blood. Therefore, the advantages of using liquid biopsy for brain tumors is still to be confirmed. The present study evaluates the ability of liquid biopsy to detect IDH1 mutations and its correlation with survival and clinical characteristics of glioma patients. Methods Blood samples obtained from glioma patients were collected after surgery prior to the adjuvant therapy. cfDNA was extracted from plasma and IDH1 p.R132H mutation analysis was performed on a digital droplet PCR. χ2-test and Cohen k were used to assess the correlation between plasma and tissue IDH1 status, while Kaplan Meier curve and Cox regression analysis were applied to survival analysis. Statistical calculations were performed by MedCalc and GraphPad Prism software. Results A total of 67 samples were collected. A concordance between IDH1 status in tissue and in plasma was found (p = 0.0024), and the presence of the IDH1 mutation both in tissue (138.8 months vs 24.4, p

FLASH-radiotherapy delivers a radiation beam a thousand times faster compared to conventional radiotherapy, reducing radiation damage in healthy tissues with an equivalent tumor response. Although not completely understood, this radiobiological phenomenon has been proved in several animal models with a spectrum of all kinds of particles currently used in contemporary radiotherapy, especially electrons. However, all the research teams have performed FLASH preclinical studies using industrial linear accelerator or LINAC commonly employed in conventional radiotherapy and modified for the delivery of ultra-high-dose-rate (UHDRs). Unfortunately, the delivering and measuring of UHDR beams have been proved not to be completely reliable with such devices. Concerns arise regarding the accuracy of beam monitoring and dosimetry systems. Additionally, this LINAC totally lacks an integrated and dedicated Treatment Planning System (TPS) able to evaluate the internal dose distribution in the case of in vivo experiments. Finally, these devices cannot modify dose-time parameters of the beam relevant to the flash effect, such as average dose rate; dose per pulse; and instantaneous dose rate. This aspect also precludes the exploration of the quantitative relationship with biological phenomena. The dependence on these parameters need to be further investigated. A promising advancement is represented by a new generation of electron LINAC that has successfully overcome some of these technological challenges. In this review, we aim to provide a comprehensive summary of the existing literature on in vivo experiments using electron FLASH radiotherapy and explore the promising clinical perspectives associated with this technology.

Radiotherapy (RT) is performed in approximately 75% of patients with cancer, and its efficacy is often hampered by the low tolerance of the surrounding normal tissues. Recent advancements have demonstrated the potential to widen the therapeutic window using “very short” radiation treatment delivery (from a conventional dose rate between 0.5 Gy/min and 2 Gy/min to more than 40 Gy/s) causing a significant increase of normal tissue tolerance without varying the tumor effect. This phenomenon is called “FLASH Effect (FE)” and has been discovered by using electrons. Although several physical, dosimetric, and radiobiological aspects need to be clarified, current preclinical “in vivo” studies have reported a significant protective effect of FLASH RT on neurocognitive function, skin toxicity, lung fibrosis, and bowel injury. Therefore, the current radiobiological premises lay the foundation for groundbreaking potentials in clinical translation, which could be addressed to an initial application of Low Energy Electron FLASH (LEE) for the treatment of superficial tumors to a subsequent Very High Energy Electron FLASH (VHEE) for the treatment of deep tumors. Herein, we report a clinical investigational scenario that, if supported by preclinical studies, could be drawn in the near future.

In recent years, FLASH radiotherapy (FLASH RT) has gained attention in preclinical studies as a potential advancement in cancer treatment. The great advantage of FLASH RT is the ultra-fast, high doses delivery that have a similar or greater effect on cancer cells while sparing normal, healthy tissue surrounding the tumor site. This is known as the FLASH effect. However, currently, there are not enough in vitro and in vivo data to transpose FLASH RT to human trials. This mini review summarizes the available in vitro data on electron beam FLASH, focusing on possible mechanisms of the FLASH effect. Current studies have focused on various types of cancer, including lung cancer, glioblastoma, uterus adenocarcinoma, cervix carcinoma, prostate carcinoma, melanoma, breast cancer, head and neck squamous cell carcinoma, and colon adenocarcinoma. Several hypotheses have been proposed to explain the biological mechanisms contributing to the to the selective FLASH effect, including differences between healthy and cancer cells in production of reactive oxygen species and free radicals, limitation of Fenton reaction caused by high Fe2+/3+ levels in tumor cells, and impaired DNA damage repair mechanisms occurring in cancer.

Despite countless papers in the field of radioresistance, researchers are still far from clearly understanding the mechanisms triggered in glioblastoma. Cancer stem cells (CSC) are important to the growth and spread of cancer, according to many studies. In addition, more recently, it has been suggested that CSCs have an impact on glioblastoma patients’ prognosis, tumor aggressiveness, and treatment outcomes. In reviewing this new area of biology, we will provide a summary of the most recent research on CSCs and their role in the response to radio-chemotherapy in GB. In this review, we will examine the radiosensitivity of stem cells. Moreover, we summarize the current knowledge of the biomarkers of stemness and evaluate their potential function in the study of radiosensitivity.

Summary: The European Society for Medical Oncology (ESMO) suggests the use of chemotherapy as neoadjuvant, adjuvant, and concomitant to surgery and radiotherapy for the treatment of oral carcinoma by depending on the cancer stage. The usual drug of choice belongs to the platinum compounds. In this context, the evaluation of the cancer behavior associated with the administration of standard or emerging cisplatin compounds supports the establishment of optimal cancer management. Here, we have assessed and compared the performance of cisplatin alone and contained in biodegradable nanocapsules on standardized chorioallantoic membrane (CAM) tumor models. The vascularized environment and optimized grafting procedure allowed the establishment of solid tumors. The treatments showed antitumor and anti-angiogenic activities together with deregulation of pivotal genes responsible of treatment resistance and tumor aggressiveness. This study further supports the significance of CAM tumor models in oncological research for the comprehension of the molecular mechanisms involved in tumor treatment response.

Abstract Background Distant Metastases from Head and Neck Squamous cell carcinomas are uncommon (9–11%) and they are usually found in the lung and less frequently in the liver, kidney and adrenals. Central nervous system (CNS) metastases are extremely rare (2–8%), and they are described mainly in patients who already have extracranial metastases. So there’s scarcity of data about their optimal management . Methods and results A patient presented CNS metastases after having been successfully treated with induction chemotherapy and definitive radiotherapy for a pyriform sinus carcinoma. The patient’s work up, treatment and outcome are described. Conclusions CNS metastases from Head and Neck carcinomas are exceptionally rare. Nevertheless, clinicians should be alert of neurological symptoms in these patients, in order to set up a timely assessment and treatment. Secondarily, given the rarity of this condition, additional research on this topic is warranted in order to improve therapeutic strategies and outcomes of such patients.

Purpose : The aim of the present study was to evaluate the effectiveness of hyaluronic acid (HA) in the prevention of acute and late vaginal toxicities after high-dose-rate (HDR) vaginal brachytherapy (BT). Material and methods : Between January 2011 and January 2015, we retrospectively analyzed 126 patients with endometrial cancer who underwent extrafascial hysterectomy with or without lymphadenectomy and adjuvant HDR-vaginal BT +/– adjuvant chemotherapy. The total dose prescription was 21 Gy in 3 fractions (one fraction for week). Vaginal ovules containing 5 mg of HA were given for whole duration of vaginal BT and for the two following weeks. Acute and late toxicities were evaluated according to CTCAE vs 4.02. Results : According to the revised FIGO 2009 classification, most tumors were in stage IA (30.9%) and in stage IB (57.9%). Thirty-three patients (26.2%) received adjuvant chemotherapy before vaginal BT. Five-year disease-free survival (DFS) and five-year overall survival (OS) were 88% and 93%, respectively. The most common grade 1-2 acute toxicities were vaginal inflammation (18 patients, 14.3%) and dyspareunia (7 patients, 5.5%). Two patients (1.6%) had more than one toxicity. Late toxicity occurred in 20 patients (15.9%). Grade 1-2 late toxicities were fibrosis (14 patients, 11.1%) and telangiectasias (7 patients, 5.5%). Six patients (4.8%) had more than one late toxicity. No grade 3 or higher acute or late toxicities were observed. Conclusions : These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery. A randomized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity.