Pre-treatment risk factors to predict early cisplatin-related nephrotoxicity in locally advanced head and neck cancer patients treated with chemoradiation: A single Institution experience

Objectives: Cisplatin is essential in the curative treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients. The assessment of risk factors to predict an early cisplatin-induced nephrotoxicity could help in better managing one of the most relevant cisplatin-related dose-limiting factors. Material and methods: We retrospectively collected data of LA-HNSCC patients treated at our Institution from 2008 to 2019. Patients received cisplatin in a curative setting concurrently with radiation. Acute Kidney Injury (AKI) was assessed as a dichotomous variable (CreaIncr) based on pre-treatment values, and values recorded at days 6-20 post-first cycle of cisplatin. Univariable logistic regression models were performed to investigate associations between CreaIncr and clinical characteristics. A multivariable logistic model on a priori selected putative covariates was performed. Results: Of the 350 LA-HNSCC treated patients, 204 were analyzed. Ninety (44 %) suffered from any grade AKI (grade I 51.1 %): out of them, 84.4 % received high-dose cisplatin (100 mg/m2 q21). On the univariable logistic regression model, male sex, age, serum uric acid, creatinine, concomitant drugs, and cisplatin schedule were significantly associated with a higher rate of AKI. At multivariable model, age (p = 0.034), baseline creatinine (p = 0.027), concomitant drugs (p = 0.043), and cisplatin schedule (one-day bolus or fractionated high-dose vs. weekly; p = 0.001) maintained their significant association. Conclusions: Identifying pre-treatment risk factors in LA-HNSCC patients may improve decision-making in a setting where cisplatin has a curative significance. A strict monitoring of AKI could avoid cisplatin dose adjustments, interruptions, and treatment delays, thus limiting a negative impact on outcomes

Port in oncology practice: 3-monthly locking with normal saline for catheter maintenance, a preliminary report

Introduction Patients with cancer need stable venous access using central vascular devices like central venous ports and peripherally inserted central catheters that can be used for a wide range of indications. Numerous flushing protocols exist including different frequencies for catheter locking to maintain catheter patency. The aim of this retrospective study was to evaluate the incidence of lumen occlusion of central venous ports in a group of adult cancer patients, adopting a policy of locking with normal saline every three months. Methods This is a single-center retrospective observational study. During follow-up, we analyzed adult cancer patients who had undergone port insertion from January 1st, 2007 to August 31st, 2014. Flushing and locking were performed every three months with a syringe containing normal saline. Results We collected data from 381 patients with ports inserted in subclavian vein (379 patients) and in the right jugular vein (2 patients). Locking was performed during 3-monthly follow-up visits. Median follow-up was 810 days (90-2700 days). Among 381 ports, 59 were removed; the reasons for removal were: end of use (45 cases), catheter rupture (9 cases), dislocation (3 cases) and catheter-related bloodstream infection (2 cases). We had no reports of lumen occlusion. Conclusions Our data suggest that locking ports with normal saline every three months is not associated with an increased risk of lumen occlusion. </jats:sec

Autophagy inhibition enhances anthocyanin-inducedapoptosis in hepatocellular carcinoma

Anthocyanins extracted from the berries of Phillyrea latifolia L., Pistacia lentiscus L., and Rubia peregrina L., three evergreen shrubs widely distributed in the Mediterranean area, were examined for their antioxidant and anticancer activity. The P. lentiscus anthocyanins showed the highest H2O2 and 1,1-diphenyl-2-picryl- hydrazil radical scavenging effects, indicating that these compounds can be considered as an alternative source of natural antioxidants for food and pharmaceutical products. Here, we also report a novel function of anthocyanins: the induction of autophagy, a process of subcellular turnover involved in carcinogenesis. Autophagy was characterized by the up-regulation of eIF2A, an autophagy inducer, and down-regulation of mTOR and Bcl-2, two autophagy inhibitors. This led to the enhanced expression of LC3-II, an autophagosome marker in mammals, and monodansyl- cadaverine incorporation into autolysosomes. Anthocya- nin-induced autophagy switched to apoptosis, as shown by the activation of Bax, cytochrome c and caspase 3, terminal deoxynucleotide transferase–mediated dUTP nick-end labeling–positive fragmented nuclei, and cells with sub-G1 DNA content, which were prevented by z-VAD. Inhibition of autophagy by either 3-methyladenine or Atg5 small interfering RNA enhanced anthocyanin- triggered apoptosis. This provided evidence that autoph- agy functions as a survival mechanism in liver cancer cells against anthocyanin-induced apoptosis and a ratio-nale for the use of autophagy inhibitors in combination with dietary chemopreventive agents. [Mol Cancer Ther 2008;7(8):2476–85

Prognostic value of relative cerebral blood volume (rCBV) in patients with recurrent glioblastoma multiforme treated with bevacizumab

BACKGROUND: To assess whether the early monitoring of the effects of bevacizumab in patients with recurrent glioblastoma multiforme (GBM) using perfusional dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) before and after the beginning of anti-angiogenic therapy is predictive of treatment response. METHODS: Thirteen patients with recurrent GBM underwent perfusion MRI with relative cerebral blood volume (rCBV) mapping before (T0) and after the beginning (T1) of bevacizumab treatment. Recurrence Regions of Interest (RoIs) were positioned on the enhancing component of tumoral tissue revealed by post-contrast T1-weighted images. The rCBV measurements on the corresponding maps were made before and after the start of the anti-angiogenic therapy. The Cox proportional hazards model and the Kaplan-Meier method were used with the log-rank test to establish whether pre- and post-bevacizumab rCBV predicted progression-free survival (PFS). We tried to assess if there was a correlation between rCBV at T0 and rCBV at T1 using the Pearson's correlation coefficient. RESULTS: In the univariable analysis, rCBV was significantly predictive of PFS at T0 (HR= 5.3, p=0.003) and at T1 (HR=4.14, p=0.04). Similarly, in the multivariate Cox model analysis, rCBV was predictive of PFS at T0 (HR=4.4, p=0.04) and T1 (HR=4.2, p=0.02). PFS was longer in patients whose rCBV was less than 4.50 ml/100g at T0 and less than 1.83 ml/100g at T1 than in patients with higher rCBV values. There was a moderate positive correlation between rCBV at T0 and rCBV at T1 (P=0.032, R=0.546). CONCLUSIONS: Despite the limited number of enrolled patients, rCBV assessed using DSC-MRI through the parameter rCBV is proved reliable in predicting the effects of anti-angiogenic treatment in patients with recurrent GBM

Abiraterone Acetate in Patients With Castration-Resistant, Androgen Receptor-Expressing Salivary Gland Cancer: A Phase II Trial

The activity of androgen-deprivation therapy (ADT) in androgen receptor-positive (AR+) salivary gland carcinomas (SGCs) has been established in the past few years. Second-line treatment in castration-resistant patients is still unknown. We investigated the activity of abiraterone acetate as second-line treatment in ADT-resistant, AR+ patients with SGC

A Simon's two-stage design trial evaluating the potential role of a kind of honey in preventing chemotherapy-hematopoietic toxicities

BACKGROUND AND AIM: Hematopoietic toxicities are a serious consequence of myelosuppressive CT that may result in dose reductions, delays or even discontinuation of CT, which, in turn, may compromise patient outcomes. Concerns about tolerability and costs of CSFs are still ongoing, therefore the potential use of supportive therapeutics agents are still of interest. EXPERIMENTAL PROCEDURE: We performed a monocentric, phase II study using Simon's two-stage design. The primary endpoint was the evaluation of the potential clinical benefit of a special kind of honey (Life-Mel Honey) administered prophylactically to reduce the incidence of hematopoietic toxicities following chemotherapy. We have enrolled patients undergoing adjuvant or first-line chemotherapy. RESULTS AND CONCLUSION: From November 2013 to May 2014 (First stage) and from November 2014 to April 2016 (Second stage), 39 patients were enrolled at our Institution. The majority of patients was male (24/39, 61.5%), medium age was 60.4 years (range 34–77 years). The median follow up was 74.5 days (SD +/- 28.5). Overall, the majority of patients could underwent their chemoterapy with a regular schedule (25/39, 64.1%), while 9/39 patients (23.1%) need to delay chemotherapy due to hematological adverse events of various grade. Ten/39 patients (25.6%) had a grade 1 neutrophils count decreased, 56.4% a grade 1 platelets count decrease and 64.1% a grade 1 hemoglobin decrease. Therefore, Life-Mel Honey showed an interesting profile to reduce hematological toxicities. The proportion of responses is sufficiently high to recommend this honey to go to a next step in the clinical trial phase

Primary Ewing's sarcoma of the sinonasal tract, eroding the ethmoid and sphenoid sinus with intracranial extension: A rare case report

Ewing's sarcoma (ES) is an aggressive tumour that may present with skeletal and extraskeletal forms. The extraskeletal form is rarely encountered in the head and neck region and is extremely rare in the sinonasal tract. This is the case report of a ES of the ethmoid sinus with intracranial and orbital extension in a 33-year-old male patient who presented with anosmia, epistaxis, reduction of visual acuity in the left eye and headache. On otorhinolaryngological clinical examination and biopsy via flexible endoscope, the lesion was misdiagnosed as ethmoid sinus carcinoma. The subsequent magnetic resonance imaging (MRI) of the brain revealed a large mass (6 77 cm) eroding the ethmoid and sphenoid sinuses, extending beyond the orbits and occupying the anterior cranial fossa with a maximum extension of ~5 cm. The patient underwent surgical resection and the microscopic examination of the specimen established the diagnosis of ES (immunohistochemically positive for CD99, neuron-specific enolase, CD56, synaptophysin, pancytokeratin, low-molecular weight cytokeratins and vimentin. The periodic acid Schiff stain exhibited strong intracytoplasmic block positivity and fluorescence in situ hybridization revealed a t(22;11) translocation. First-line chemotherapy was administered for 3 cycles; however, on restaging MRI, local disease progression was diagnosed. The patient received radiotherapy and second-line chemotherapy for 6 cycles. At 15 months after the diagnosis, the patient remains recurrence-free and maintains a good functional status and quality of life